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1.
Aging (Albany NY) ; 16(10): 8472-8483, 2024 05 26.
Artículo en Inglés | MEDLINE | ID: mdl-38809424

RESUMEN

OBJECTIVE: To investigate the role of the EGFR/MAPK signaling pathway in PM2.5 in promoting the MUC5AC hypersecretion in airway and exacerbating airway inflammation. METHODS: By establishing rat model exposed to PM2.5, overexpressing miR-133b-5p and Claudin1, the content of IL-1 and TNF-α in serum were detected by ELISA, the pathology of lung tissue was observed by HE staining, p-EGFR, Claudin1, MUC5AC, p-ERK1/2, p-JNK, p-p38 in rats lung tissue were detected by immunohistochemical and WB, the expression level of miR-133b-5p in rats lung tissue were detected by qPCR. RESULTS: After the rats were exposed to PM2.5, the content of inflammatory factors in serum increased, the inflammatory damage of lung tissues occurred, the expression of miR-133b-5p was down-regulated, and the expression of MUC5AC protein was increased. The ELISA test results showed that the expression of IL-1 and TNF-α in the model group was significantly higher than that in the control group, and the model +AG1478 treatment group was down-regulated compared with the model group, and the +miR-133b-5p agomir treatment group was significantly lower than that in the control group, the model group and the model +Claudin1 overexpression blank load group, and the model +Claudin1 overexpression group was down-regulated compared with the model group and the model +Claudin1 overexpression blank load group. The protein detection results showed that the expression of p-EGFR, MUC5AC, p-ERK1/2, p-JNK and p-p38 proteins was increased and the expression of Claudin1 protein was decreased in the model group compared with the control group. In the model + AG1478 treatment group, model + miR-133b-5p agomir treatment group and model + Claudin1 overexpression group, compared with the model group, p-EGFR, MUC5AC, p-ERK1/2, p-JNK, p-p38 protein expression was down-regulated, and Claudin1 protein expression was up-regulated. CONCLUSIONS: PM2.5 inhibited the expression of miR-133b-5p to activate the EGFR/MAPK signal pathway, induce the hypersecretion of MUC5AC, thus aggravating PM2.5-related airway inflammation in rats.


Asunto(s)
Claudina-1 , Receptores ErbB , MicroARNs , Mucina 5AC , Material Particulado , Animales , MicroARNs/metabolismo , MicroARNs/genética , Mucina 5AC/metabolismo , Mucina 5AC/genética , Ratas , Receptores ErbB/metabolismo , Receptores ErbB/genética , Material Particulado/toxicidad , Claudina-1/metabolismo , Claudina-1/genética , Masculino , Ratas Sprague-Dawley , Pulmón/metabolismo , Pulmón/patología , Moco/metabolismo , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismo , Sistema de Señalización de MAP Quinasas
2.
ACS Biomater Sci Eng ; 10(5): 3069-3085, 2024 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-38578110

RESUMEN

Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. Drug delivery to the brain through the blood-brain barrier (BBB) is a significant challenge in PD treatment. Exosomes, which can efficiently traverse the BBB, which many drugs cannot penetrate, are ideal natural carriers for drug delivery. In this study, the BBB shuttle peptide was modified on the exosome surfaces. Three types of exosomes were constructed, each modified with a distinct peptide (RVG29, TAT, or Ang2) and loaded with miR-133b. The safety and brain-targeting capabilities of these peptide-modified exosomes were then evaluated. Finally, the mechanism by which RVG29-Exo-133b regulates the RhoA-ROCK signaling pathway was investigated. The findings indicate that the three peptide-modified exosomes were adequately tolerated, safe, and effectively assimilated in vivo and ex vivo, with RVG29 exhibiting superior targeting to the brain. Furthermore, RVG29-Exo-133b decreased the phosphorylation level of the Tau protein by targeting the RhoA-ROCK signaling pathway. It also enhanced the motor function in mice with PD, thereby reducing the degree of depression, improving dopaminergic neuron function, and attenuating 6-OHDA-induced nerve damage. In this study, we developed a stable drug delivery mechanism that targets the intracerebral region using exosomes. Furthermore, a novel strategy was developed to manage PD and can potentially serve as a preclinical basis for utilizing exosomes in the diagnosis and treatment of neurodegenerative conditions.


Asunto(s)
Exosomas , MicroARNs , Enfermedad de Parkinson , Transducción de Señal , Quinasas Asociadas a rho , Proteína de Unión al GTP rhoA , Exosomas/metabolismo , Animales , Quinasas Asociadas a rho/metabolismo , Quinasas Asociadas a rho/genética , MicroARNs/metabolismo , MicroARNs/genética , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/genética , Proteína de Unión al GTP rhoA/metabolismo , Proteína de Unión al GTP rhoA/genética , Ratones , Masculino , Ratones Endogámicos C57BL , Humanos , Péptidos/metabolismo , Barrera Hematoencefálica/metabolismo
3.
Biomed Mater ; 19(3)2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38422520

RESUMEN

Corneal stromal injury is a common surgical disease. With the development of tissue engineering materials, many artificial corneal scaffolds have been developed to replace allograft corneal transplantation and solve the problem of corneal donor shortage. However, few researchers have paid attention to corneal stromal wound healing. Herein, a nanocomposite of amino modified mesoporous bioactive glass (MBG-NH2) and microRNA-133b (miR-133b) was introduced into the patterned collagen films to achieve corneal stromal injury repair. MBG-NH2nanoparticles as a nano delivery carrier could efficiently load miR-133b and achieve the slow release of miR-133b. The physicochemical properties of collagen films were characterized and found the microgrooved collagen films loaded with miR-133b@MBG-NH2nanoparticles possessed similar swelling properties, optical clarity, and biodegradability to the natural cornea.In vitrocell experiments were also conducted and proved that the patterned collagen films with miR-133b@MBG-NH2possessed good biocompatibility, and miR-133b@MBG-NH2nanoparticles could be significantly uptake by rabbit corneal stromal cells (RCSCs) and have a significant impact on the orientation, proliferation, migration, and gene expression of RCSCs. More importantly, the patterned collagen films with miR-133b@MBG-NH2could effectively promote the migration of RCSCs and accelerate wound healing process, and down-regulate the expression levels ofα-SMA, COL-I, and CTGF genes associated with myofibroblast differentiation of corneal stromal cells, which has a potential application prospect in the repair of corneal stromal injury.


Asunto(s)
Colágeno , MicroARNs , Animales , Conejos , Ingeniería de Tejidos/métodos , Córnea , Sustancia Propia , Vidrio/química , Andamios del Tejido/química , Porosidad
4.
Microrna ; 13(1): 56-62, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38231064

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in the world. Noncoding RNAs or microRNAs (miRNAs; miRs) biomarkers can play a role in cancer carcinogenesis and progression. Specific KRAS and EGFR mutation are associated with CRC development playing a role in controlling the cellular process as epigenetic events. Circulating serum miRs can serve for early diagnosis, monitoring, and prognosis of CRC as biomarkers but it is still unclear, clinically. OBJECTIVE: To determine potential biomarkers of circulating serum miR-133b and miR-206 in CRC patients Methods: Bioinformatic prediction of microRNA was screened followed by TargetScanHuman7.2, miRTar2GO, miRDB, MiRanda, and DIANA-microT-CDS. Forty-four CRC serum (19 locally advanced, 23 distant advanced CRC) and 12 normal serum samples were subsequently extracted for RNA isolation, cDNA synthesis, and miR validation. The candidate circulating serum miR-133b and miR-206 were validated resulting in a relative expression via quantitative RT-PCR. Relative expression was normalized to the spike-internal control and compared to normal samples as 1 using the -2ΔΔCt method in principle. RESULTS: Our results represented 9 miRs of miR-206, miR-155-5p, miR-143-3p, miR-193a-3p, miR-30a- 5p, miR-30d-5p, miR-30e-5p, miR-543, miR-877-5p relate to KRAS-specific miRs, whereas, 9 miRs of miR-133b, miR-302a-3p, miR-302b-3p, miR-302d-3p, miR-302e, miR-520a-3p, miR-520b, miR-520c- 3p and miR-7-5p relevance to EGFR-specific miRs by using the bioinformatic prediction tools. Our results showed a decreased expression level of circulating serum miR-133b as well as miR-206 associating with CRC patients (local and advanced metastasis) when compared to normal (P < 0.05), significantly. CONCLUSION: The circulating serum miR-133b and miR-206 can serve as significant biomarkers for monitoring the clinical outcome of progression with metastatic CRC patients. Increased drug-responsive CRC patients associated with crucial molecular intervention should be further explored, clinically.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Colorrectales , Progresión de la Enfermedad , MicroARNs , Humanos , MicroARNs/sangre , MicroARNs/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/patología , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Masculino , Femenino , Persona de Mediana Edad , Regulación Neoplásica de la Expresión Génica/genética , Regulación hacia Abajo/genética , Anciano , Pronóstico , Metástasis de la Neoplasia , Adulto
5.
Clin Med Insights Oncol ; 17: 11795549231219502, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38144543

RESUMEN

Background: Evaluation of biological changes at the molecular level has important clinical implications for improving the survival rate of esophageal squamous cell carcinoma (ESCC). Therefore, we plan to analyze and elucidate the expression of microRNA-133b (miR-133b), M2 pyruvate kinase (PKM2), and signal transducer and activator of transcription 3 (STAT3) in ESCC and their associated clinicopathological significance. Methods: The 72 patients with ESCC were selected as the experimental study group. Normal adjacent tissues (NAT) were matched as the control group. In this study, in situ hybridization was used to detect the expression of miR-133b in ESCC, and tissue expressions of PKM2 and STAT3 were detected by immunohistochemistry, and literature review was conducted. Results: Studies had shown that the positive expression of miR-133b in NAT was significantly higher than that in ESCC (χ2 = 9.007, P = .003). PKM2 and STAT3 in ESCC had a significantly higher positive expression levels than those of NAT (χ2 = 56.523, P = .000; χ2 = 72.939, P = .000). From correlation analysis, there was a negative correlation between miR-133b and PKM2(r = -0.515, P < .001), a negative correlation between miR-133b and STAT3(r = -0.314, P = .007), and a positive correlation between PKM2 and STAT3(r = 0.771, P < .001). Conclusions: In ESCC, our study demonstrated that downregulation of miR-133b and upregulation of PKM2 and STAT3. We predict that miR-133b may inhibit the STAT3 pathway by downregulating PKM2.

6.
Biomedicines ; 11(9)2023 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-37760864

RESUMEN

Prompt diagnosis of ST-segment elevation myocardial infarction (STEMI) is essential for initiating timely treatment. MicroRNAs have recently emerged as biomarkers in cardiovascular diseases. This study aimed to evaluate the discriminatory capacity of serum microRNAs in identifying an ischemic origin in patients presenting with chest discomfort to the Emergency Department. The study included 98 participants (78 with STEMI and 20 with nonischemic chest discomfort). Significant differences in the expression levels of miR-133b, miR-126, and miR-155 (but not miR-1, miR-208, and miR-208b) were observed between groups. miR-133b and miR-155 exhibited 97% and 93% sensitivity in identifying STEMI patients, respectively. miR-126 demonstrated a specificity of 90% in identifying STEMI patients. No significant associations were found between microRNAs and occurrence of major adverse cardiovascular events (MACE). However, patients with MACE had higher levels of interleukin (IL)-15, IL-21, IFN-γ-induced protein-10, and N-terminal pro B-type natriuretic peptide compared to non-MACE patients. Overall, there were significant associations among the expression levels of microRNAs. However, microRNAs did not demonstrate associations with either inflammatory markers or cardiovascular risk scores. This study highlights the potential of microRNAs, particularly miR-133b and miR-126, as diagnostic biomarkers for distinguishing patients with STEMI from those presenting with nonischemic chest discomfort to the Emergency Department.

7.
Mol Cell Biochem ; 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37522976

RESUMEN

Hsa_circ_0071589 can exacerbate the malignant behavior of colorectal cancer (CRC) cells. However, its function in stemness and oxaliplatin (OXP) resistance of CRC cells remains unclear. To assess the function of hsa_circ_0071589 in stemness and OXP resistance of CRC cells. Western blotting and qRT-PCR were applied to assess protein and mRNA levels. The association between hsa_circ_0071589, miR-133b and SOX13 was explored via a correlation analysis. Sphere formation was used to assess cell stemness. Meanwhile, the viability of CRC cells and OXP-resistant CRC cells was evaluated with the MTT assay. Cell stemness marker (CD133) levels and apoptosis of CRC cells and OXP-resistant CRC cells were tested using flow cytometry. The ALDH level was investigated using the related detection kit. In addition, the association between hsa_circ_0071589 and miR-133b and SOX13 was investigated using the RIP and dual luciferase assay. Finally, in vivo experiments were performed to detect the function of hsa_circ_0071589 in CRC, and the levels of SOX13, Ki67, and CD44 in mice were evaluated via immunohistochemistry staining. The expression of hsa_circ_0071589 and SOX13 was upregulated in CRC, whereas the expression of miR-133b was downregulated. Hsa_circ_0071589 knockdown significantly inhibited CRC stemness via the mediation of miR-133b. Moreover, hsa_circ_0071589 silencing significantly sensitized CRC cells to OXP by upregulating miR-133b. SOX13 was the direct target of miR-133b, and miR-133b could attenuate stemness and OXP resistance in CRC cells by targeting SOX13. Notably, hsa_circ_0071589 knockdown inhibited tumor growth and decreased OXP resistance in mice with CRC. Hsa_circ_0071589 aggravates stemness and OXP resistance by sponging miR-133b to indirectly target SOX13 in CRC. Thus, our study might present a novel treatment strategy against OXP-resistant CRC.

8.
Cancer Med ; 12(8): 9826-9842, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36846934

RESUMEN

BACKGROUND: Forkhead box L2 (FOXL2) has been recognized as a transcription factor in the progression of many malignancies, but its role in non-small cell lung cancer (NSCLC) remains unclear. This research clarified on the role of FOXL2 and the specific molecular mechanism in NSCLC. METHODS: RNA and protein levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting assays. Cell proliferation was examined by cell counting kit-8 (CCK-8) and clonogenic assays. Transwell and wound healing assays were used to detect cell invasion and migration. Cell cycle alterations were assessed by flow cytometry. The relationship between FOXL2 and miR-133b was verified by dual-luciferase reporter assays. In vivo metastasis was monitored in the tail vein-injected mice. RESULTS: FOXL2 was upregulated in NSCLC cells and tissues. Downregulation of FOXL2 restrained cell proliferation, migration, and invasion and arrested the cell cycle of NSCLC cells. Moreover, FOXL2 promoted the epithelial-mesenchymal transition (EMT) process of NSCLC cells by inducing the transforming growth factor-ß (TGF-ß)/Smad signaling pathway. miR-133b directly targeted the 3'-UTR of FOXL2 and negatively regulated FOXL2 expression. Knockdown of FOXL2 blocked metastasis in vivo. CONCLUSIONS: miR-133b downregulates FOXL2 by targeting the 3'-UTR of FOXL2, thereby inhibiting cell proliferation, EMT and metastasis induced by the TGF-ß/Smad signaling pathway in NSCLC. FOXL2 may be a potential molecular target for treating NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , Animales , Ratones , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , MicroARNs/genética , MicroARNs/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Factor de Crecimiento Transformador beta/metabolismo , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Transición Epitelial-Mesenquimal/genética
9.
Am J Physiol Heart Circ Physiol ; 324(5): H598-H609, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36827227

RESUMEN

Insulin resistance (IR) is one of the hallmarks of heart failure (HF). Abnormalities in skeletal muscle (SM) metabolism have been identified in patients with HF. However, the underlying mechanisms of IR development in SM in HF are poorly understood. Herein, we hypothesize that HF upregulates miR-133b in SM and in turn alters glucose metabolism and the propensity toward IR. Mitochondria isolated from SM of mice with HF induced by transverse aortic constriction (TAC) showed lower respiration and downregulation of muscle-specific components of the tricarboxylic acid (TCA) cycle, AMP deaminase 1 (AMPD1), and fumarate compared with those from control animals. RNA-Seq and subsequent qPCR validation confirmed upregulation of SM-specific microRNA (miRNA), miR-133b, in TAC versus sham animals. miR-133b overexpression alone resulted in significantly lower mitochondrial respiration, cellular glucose uptake, and glycolysis along with lower ATP production and cellular energy reserve compared with the scramble (Scr) in C2C12 cells. miR-133b binds to the 3'-untranslated region (UTR) of KLF15, the transcription factor for the insulin-sensitive glucose transporter, GLUT4. Overexpression of miR-133b lowers GLUT4 and lowers pAkt in presence of insulin in C2C12 cells. Finally, lowering miR-133b in primary skeletal myocytes isolated from TAC mice using antagomir-133b reversed the changes in KLF15, GLUT4, and AMPD1 compared with the scramble-transfected myocytes. Taken together, these data demonstrate a role for SM miR-133b in altered glucose metabolism in HF and suggest the therapeutic potential in HF to improve glucose uptake and glycolysis by restoring GLUT4 abundance. The data uncover a novel mechanism for IR and ultimately SM metabolic abnormalities in patients with HF.NEW & NOTEWORTHY Heart failure is associated with systemic insulin resistance and abnormalities in glucose metabolism but the underlying mechanisms are poorly understood. In the skeletal muscle, the major peripheral site of glucose utilization, we observe an increase in miR-133b in heart failure mice, which reduces the insulin-sensitive glucose transporter (GLUT4), glucose uptake, and metabolism in C2C12 and in myocytes. The antagomir for miR-133b restores GLUT4 protein and markers of metabolism in skeletal myocytes from heart failure mice demonstrating that miR-133b is an exciting target for systemic insulin resistance in heart failure and an important player in the cross talk between the heart and the periphery in the heart failure syndrome.


Asunto(s)
Insuficiencia Cardíaca , Resistencia a la Insulina , MicroARNs , Ratones , Animales , Resistencia a la Insulina/genética , Antagomirs/metabolismo , Músculo Esquelético/metabolismo , Glucosa/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Insulina/metabolismo , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/metabolismo , Proteínas Facilitadoras del Transporte de la Glucosa/metabolismo , Transportador de Glucosa de Tipo 4/genética , Transportador de Glucosa de Tipo 4/metabolismo
10.
Gynecol Obstet Invest ; 87(5): 305-315, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36198257

RESUMEN

OBJECTIVE: Preeclampsia (PE) is the most common gestational disease related to various biomolecules, including circular RNA. Hsa_circ_0088196 (circ_0088196) was aberrantly upregulated in PE tissues. DESIGN: This study focused on the further exploration of circ_0088196 in PE. METHODS: Circ_0088196, microRNA-133b (miR-133b), and AHNAK Nucleoprotein (AHNAK) levels were examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). EDU assay was used for proliferation detection. Cell cycle and apoptosis were analyzed using flow cytometry. Wound healing assay and transwell assay were performed to assess migration and invasion. The protein levels were determined via Western blot. Target analysis was conducted through dual-luciferase reporter assay and RNA pull-down assay. RESULTS: Circ_0088196 upregulation was detected in PE patients. The knockdown of circ_0088196 induced the promotion of proliferation, cell cycle, migration, and invasion but not the inhibition of apoptosis in trophoblastic cells. Then, circ_0088196 was found to act as a sponge of miR-133b in HTR-8/SVneo cells. The inhibition of miR-133b abolished the regulation of si-circ_0088196 in trophoblastic cells. In addition, miR-133b targeted AHNAK and circ_0088196 evoked the expression change of AHNAK by sponging miR-133b. The function of circ_0088196 was also achieved by regulating AHNAK in trophoblastic cells. LIMITATIONS: The role of circ_0088196 in PE was not verified by in vivo experiments. CONCLUSION: The current evidence demonstrated that circ_0088196 knockdown facilitated trophoblastic cell development by regulating the levels of miR-133b and AHNAK, suggesting that circ_0088196 promoted the PE progression via the miR-133b/AHNAK axis.


Asunto(s)
Proteínas de la Membrana , MicroARNs , Preeclampsia , ARN Circular , Femenino , Humanos , Embarazo , Apoptosis/genética , Proliferación Celular/genética , Regulación hacia Abajo , Proteínas de la Membrana/genética , MicroARNs/genética , Proteínas de Neoplasias , Preeclampsia/genética , Regulación hacia Arriba , ARN Circular/genética
11.
J Gene Med ; 24(11): e3453, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36181243

RESUMEN

BACKGROUND: The Warburg effect is a characteristic tumor cell behavior regarded as one of the cancer hallmarks and promotes tumor progression by promoting glucose uptake and lactate production. Long non-coding RNAs (lncRNAs) had been reported to emerge as a vital function in cancer development. The present research is designed to investigate the underlying molecular mechanism of lncRNA TMEM147 antisense RNA 1 (TMEM147-AS1) on aerobic glycolysis in prostatic carcinoma. METHODS: lncRNA TMEM147-AS1, miR-133b and ZNF587 levels in prostatic carcinoma tissues and cells were detected by a polymerase chain reaction or western blot assays. Cell viability or invasion was determined by Edu (i.e. 5-ethynyl-2'-deoxyuridine), MTT (i.e. 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) or transwell assays. Hematoxylin and eosin and immunohistochemical staining were applied for histopathological examination. Tumor xenograft model was employed to investigate tumor growth in vivo. The combinative relationship between TMEM147-AS1 or ZNF587 and miR-133b was confirmed by a luciferase reporter assay. RESULTS: TMEM147-AS1 and ZNF587 were up-regulated in prostatic carcinoma tissues and cells. Knockdown of TMEM147-AS1 or ZNF587 within prostate cancer cells significantly restrained cell viability, invasion and aerobic glycolysis in vitro and suppressed the neoplasia of prostatic carcinoma in vivo. miR-133b was directly targeted in both TMEM147-AS1 and ZNF587. Overexpression of miR-133b restrained prostate cancer cell viability, invasion and aerobic glycolysis. TMEM147-AS1 competitively targeted miR-133b, therefore counteracting miR-133b-mediated repression on ZNF587. CONCLUSIONS: TMEM147-AS1 plays a tumor-promoting action in prostatic carcinoma aerobic glycolysis via affecting the miR-133b/ZNF587 axis, therefore regulating prostatic carcinoma cells invasion and proliferation. These outcomes implied that TMEM147-AS1 could be an effective treatment strategy for further study of prostatic carcinoma.


Asunto(s)
Carcinoma , MicroARNs , Neoplasias de la Próstata , ARN Largo no Codificante , Humanos , Masculino , Carcinoma/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Neoplasias de la Próstata/genética , ARN Largo no Codificante/genética
12.
Foods ; 11(17)2022 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-36076875

RESUMEN

Resveratrol (RES) has a wide range of biological and pharmacological activities with various health benefits for humans as a food additive. In animal production, RES has been considered a potential functional feed additive for producing high-quality pork. Long noncoding RNAs (lncRNAs) have emerged as essential regulators of fat metabolism, and phytochemicals can regulate fat metabolism through lncRNA. However, it is unclear whether RES can improve back-fat thickness by regulating lncRNA. In this study, we identified a novel lncRNA, which was named a long intergenic non-protein coding RNA, a regulator of fat metabolism (LincRNA-ROFM), from our previous lncRNA sequencing data. LincRNA-ROFM can inhibit adipocyte proliferation and differentiation. In-depth analyses showed that LincRNA-ROFM acts as a molecular sponge for miR-133b, and adiponectin (AdipoQ) is a direct target of miR-133b in porcine preadipocytes. In addition, the expression of LincRNA-ROFM was positively correlated with AdipoQ. RES can promote the expression of LincRNA-ROFM by PPARα and C/EBPα. Altogether, our research showed that LincRNA-ROFM acts as a ceRNA to sequester miR-133b and is upregulated by RES, leading to heightened AdipoQ expression, and thus decreased adipocyte proliferation and differentiation, which reduces back-fat thickness of pigs. Taken together, the RES/LincRNA-ROFM/miR-133b/AdipoQ regulatory network preliminarily explains the mechanism of action of RES in inhibiting fat deposition, which provides new insight into the downstream mechanism of RES inhibition of fat deposits by regulating the lncRNA.

13.
J Cell Mol Med ; 26(17): 4678-4685, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35880500

RESUMEN

Becker muscular dystrophy (BMD) is an X-linked neuromuscular disorder due to mutation in the DMD gene, encoding dystrophin. Despite a wide clinical variability, BMD is characterized by progressive muscle degeneration and proximal muscle weakness. Interestingly, a dysregulated expression of muscle-specific microRNAs (miRNAs), called myomirs, has been found in patients affected with muscular dystrophies, although few studies have been conducted in BMD. We analysed the serum expression levels of a subset of myomirs in a cohort of 29 ambulant individuals affected by BMD and further classified according to the degree of alterations at muscle biopsy and in 11 age-matched healthy controls. We found a significant upregulation of serum miR-1, miR-133a, miR-133b and miR-206 in our cohort of BMD patients, supporting the role of these miRNAs in the pathophysiology of the disease, and we identified serum cut-off levels discriminating patients from healthy controls, confiming the potential of circulating miRNAs as promising noninvasive biomarkers. Moreover, serum levels of miR-133b were found to be associated with fibrosis at muscle biopsy and with patients' motor performances, suggesting that miR-133b might be a useful prognostic marker for BMD patients. Taken together, our data showed that these serum myomirs may represent an effective tool that may support stratification of BMD patients, providing the opportunity of both monitoring disease progression and assessing the treatment efficacy in the context of clinical trials.


Asunto(s)
MicroARN Circulante , MicroARNs , Distrofia Muscular de Duchenne , Biomarcadores , Progresión de la Enfermedad , Humanos , MicroARNs/genética , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/metabolismo
14.
Am J Cancer Res ; 12(6): 2465-2491, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35812058

RESUMEN

Long non-coding RNAs (lncRNAs) were confirmed to be involved in regulating various malignant behaviors of tumor cells in prostate cancer (PCa). Using The Cancer Genome Atlas (TCGA) prostate adenocarcinoma datasets, several endogenous competing RNA (ceRNA) networks of lncRNA/miRNA/mRNA associated with the progression-free survival (PFS) and Gleason score (GS) were identified using bioinformatics analysis. lncRNA AC004447.2 (lncHUPC1, ENSG00000269131)/miR-133b/serologically defined colon cancer antigen-3 (SDCCAG3) was a newly identified ceRNA network that affected cell growth and apoptosis in PCa. Using q-PCR, lncHUPC1 and SDCCAG3 were found to be up-regulated in PCa cells, while miR-133b was down-regulated. The same results were found in tissue samples from 70 PCa cases. It was confirmed that the knockdown of lncHUPC1 increased the expression of miR-133b and decreased that of SDCCAG3, which further increased apoptosis and inhibited cell growth, while the miR-133b inhibitor partially reversed these effects. After transfection with miR-133b mimic after lncHUPC1-knockdown, the expression of miR-133b increased while that of SDCCAG3 reduced, and the apoptosis of the cells was more obvious and the growth of the cells was slower. Therefore, lncHUPC1 was confirmed to regulate SDCCAG3 by binding to miR-133b. Additionally, we found that the transcription factor Forkhead Box A1 (FOXA1) directly bound to the promoter of lncHUPC1 to activate it. In conclusion, the ceRNA network of lncHUPC1/miR-133b/SDCCAG3 affected the growth and apoptosis of PCa cells, and FOXA1 may be involved in the process as a transcription factor of lncHUPC1.

15.
J Obstet Gynaecol ; 42(7): 3086-3093, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35861544

RESUMEN

Circular RNAs (circRNAs) have been found to play important roles in drug resistance of human neoplasms. The aim of this study was to explore the effect of circ_0005273 on cisplatin (DDP) resistance of cervical cancer (CC) cells and identify its underlying mechanism. The quantitative real-time polymerase chain reaction (qRT-PCR) was performed to analyse circ_0005273 and miR-133b expressions, and cell counting kit-8 (CCK-8), Hoechst 33258 staining and caspase-3 activity analysis were performed to evaluate cell proliferation and apoptosis. Luciferase reporter, RNA binding protein immunoprecipitation (RIP) and RNA pull down assays were applied to explore the interaction between circ_0005273 and miR-133b. Our research showed that circ_0005273 and miR-133b expressions were upregulated and downregulated in DDP-resistant CC cancer tissues and cell lines, respectively. Both of circ_0005273 and miR-133b levels were correlated with FIGO stage, DDP status and overall survival rates. Knockdown of circ_0005273 enhanced the sensitivity of DDP-resistant CC cells to DDP by inhibiting cell proliferation and promoting cell apoptosis. Furthermore, circ_0005273 acts as a competing endogenous RNA to modulate miR-133b expression. Downregulation of miR-133b partly reversed the DDP sensitivity of circ_0005273 knockdown in DDP-resistant CC cells. In summary, our study elucidated the role of circ_0005273/miR-133b axis in DDP resistance of CC cells, which might be a potential therapeutic target for DDP-resistant CC patients. Impact StatementWhat is already known on this subject? The detailed regulatory mechanisms underlying DDP chemoresistance are still unclear. Recently, literatures reported that circ_0005273 exerts a regulatory role in the tumorigenesis and progression of human cancers including thyroid carcinoma, pancreatic carcinoma, colorectal carcinoma and breast carcinoma.What do the results of this study add? Circ_0005273 contributes to the DDP resistance of CC cells via sponging miR-133b.What are the implications of these findings for clinical practice and/or further research? The results help to reverse DDP chemoresistance, and the circ_0005273/miR-133b axis might be a potential therapeutic target for DDP-resistant CC patients.


Asunto(s)
MicroARNs , ARN Circular , Neoplasias de la Tiroides , Neoplasias del Cuello Uterino , Femenino , Humanos , Línea Celular Tumoral , Cisplatino/farmacología , Cisplatino/uso terapéutico , MicroARNs/genética , ARN Circular/genética , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/genética
16.
Mol Cancer ; 21(1): 140, 2022 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-35773744

RESUMEN

BACKGROUND: Aberrant expression of circular RNAs (circRNAs) contributes to the initiation and progression of human malignancies, but the underlying mechanisms remain largely elusive. METHODS: High-throughput sequencing was performed to screen aberrantly expressed circRNAs or miRNAs in colorectal cancer (CRC) and adjacent normal tissues. A series of gain- and loss-of-function studies were conducted to evaluate the biological behaviors of CRC cells. RNA pulldown, mass spectrometry, RIP, qRT-PCR, Western blot, luciferase reporter assays and MeRIP-seq analysis were further applied to dissect the detailed mechanisms. RESULTS: Here, a novel circRNA named circEZH2 (hsa_circ_0006357) was screened out by RNA-seq in CRC tissues, whose expression is closely related to the clinicpathological characteristics and prognosis of CRC patients. Biologically, circEZH2 facilitates the proliferation and migration of CRC cells in vitro and in vivo. Mechanistically, circEZH2 interacts with m6A reader IGF2BP2 and blocks its ubiquitination-dependent degradation. Meanwhile, circEZH2 could serve as a sponge of miR-133b, resulting in the upregulation of IGF2BP2. Particularly, circEZH2/IGF2BP2 enhances the stability of CREB1 mRNA, thus aggravating CRC progression. CONCLUSIONS: Our findings not only reveal the pivotal roles of circEZH2 in modulating CRC progression, but also advocate for attenuating circEZH2/miR-133b/IGF2BP2/ CREB1 regulatory axis to combat CRC.


Asunto(s)
Neoplasias Colorrectales , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , MicroARNs , ARN Circular , Proteínas de Unión al ARN , Línea Celular Tumoral , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo
17.
J Cell Mol Med ; 26(13): 3636-3647, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35638462

RESUMEN

Studies have shown that SQLE is highly expressed in a variety of tumours and promotes tumour progression. However, the role of SQLE in pancreatic cancer (PC) has not been reported. Here, we aim to study the role and molecular mechanism of SQLE in PC. Immunohistochemistry and functional experiments showed that SQLE was highly expressed in PC tissues and promoted the proliferation and invasion of PC cells. Terbinafine, an inhibitor of SQLE, inhibited this effect. In order to further study the upstream mechanism that regulates SQLE, we used bioinformatics technology to lock miR-133b and lncRNA-TTN-AS. In situ hybridization was used to detect the expression of miR-133b and lncRNA-TTN-AS1 in PC tissues. The luciferase reporter gene experiment was used to confirm the binding of miR-133b and lncRNA-TTN-AS1. The results showed that miR-133b was down-regulated in PC tissues and negatively correlated with the expression of SQLE. LncRNA-TTN-AS1 was upregulated in pancreatic cancer tissues and positively correlated with the expression of SQLE. Luciferase gene reporter gene analysis confirmed lncRNA-TTN-AS1 directly binded to miR-133b. Therefore, we propose that targeting the lncRNA-TTN-AS1/miR-133b/SQLE axis is expected to provide new ideas for the clinical treatment of PC patients.


Asunto(s)
MicroARNs , Neoplasias Pancreáticas , ARN Largo no Codificante , Escualeno-Monooxigenasa , Humanos , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Conectina/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , ARN Largo no Codificante/genética , Escualeno-Monooxigenasa/genética , Neoplasias Pancreáticas
18.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(4): 407-415, 2022 Apr 28.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-35545336

RESUMEN

OBJECTIVES: Bladder cancer is one of the most common urothelial tumors with high incidence and mortality rates. Although it has been reported that microRNA (miR)-133b can regulate tumorigenesis of bladder cancer, the mechanism remains unclear. Sex-determining region Y-box transcription factor 4 (SOX4) exhibits an important role in tumorigenesis, but it is unclear whether SOX4 and miR-133b are associated with regulation of pathogenesis of bladder cancer. This study aims to determine the expressions of SOX4 and miR-133b in bladder cancer tissues and cells, investigate their effects on the proliferation, colony formation, and invasion of bladder cancer cells, and to explore the association between miR-133b and SOX4 in regulating biological featurss of bladder cancer cells. METHODS: The bladder cancer and adjacent tissue samples of 10 patients who underwent surgical resection in the Second Xiangya Hospital of Central South Universty from Januray to June 2015 were obtained. The levels of miR-133b were tested by real-time PCR, and the protein levels of SOX4 were evaluated using Western blotting in bladder cancer tissues, matched adjacent tissues, and cell lines. The correlation between miR-133b expression and SOX4 expression in bladder cancer tissues was analyzed. Using the online database TargetScan, the relationship between SOX4 and miR-133b was predicted. MiR-133b mimics, miR-133b inhibitor, and short hairpin RNA (shRNA)-SOX4 were transfected into T24 cells by Lipofectamine 2000. The relationship between miR-133b and SOX4 was also verified by a dual-luciferase reporter assay. The proliferation of T24 cells cultured for 0, 12, 48, 72, and 96 h was evaluated by cell counting kit-8 (CCK-8) assay. The colony formation capacity of bladder cancer cells was tested after 14-day culture, and cell invasion capacity was evaluated with Transwell invasion assay. RESULTS: Bladder cancer tissue and bladder cancer cells had low level of miR-133b but high level of SOX4, compared with matched adjacent tissues and normal bladder epithelial cells. A negative correlation between miR-133b mRNA and SOX4 protein levels in bladder cancer tissues was also found (r=-0.84). The results of online database TargetScan showed that miR-133b targets at SOX4, and overexpression of miR-133b significantly attenuated the expression of SOX4 in T24 cells. Both overexpression of miR-133b and knockdown of SOX4 significantly inhibited the proliferation, colony formation, and invasion capacity of bladder cancer cells in vitro. SOX4 down-regulation restored the effects of miR-133b inhibitor on the proliferation, colony formation, and invasion capacity of T24 cells. CONCLUSIONS: The up-regulation of SOX4 contributes to the progression of bladder cancer, and miR-133b can regulate the proliferation, colony formation, and invasion of bladder cancer cells via inhibiting SOX4.


Asunto(s)
MicroARNs , Factores de Transcripción SOXC , Neoplasias de la Vejiga Urinaria , Carcinogénesis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Células Epiteliales/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , Factores de Transcripción SOXC/genética , Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/genética
19.
Biomedicines ; 10(3)2022 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-35327465

RESUMEN

Based on our original RNA sequence-based microRNA (miRNA) signatures of head and neck squamous cell carcinoma (HNSCC), it was revealed that the expression levels of miR-1-3p, miR-206, miR-133a-3p, and miR-133b were significantly suppressed in cancer specimens. Seed sequences of miR-1-3p/miR-206 and miR-133a-3p/miR-133b are identical. Interestingly, miR-1-3p/miR-133a-3p and miR-206/miR-133b are clustered in the human genome. We hypothesized that the genes coordinately controlled by these miRNAs are closely involved in the malignant transformation of HNSCC. Our in silico analysis identified a total of 28 genes that had putative miR-1-3p/miR-133a-3p and miR-206/miR-133b binding sites. Moreover, their expression levels were upregulated in HNSCC tissues. Multivariate Cox regression analyses showed that expression of PFN2 and PSEN1 were independent prognostic factors for patients with HNSCC (p < 0.05). Notably, four miRNAs (i.e., miR-1-3p, miR-206, miR-133a-3p, and miR-133b) directly bound the 3'untranslated region of PFN2 and controlled expression of the gene in HNSCC cells. Overexpression of PFN2 was confirmed in clinical specimens, and its aberrant expression facilitated cancer cell migration and invasion abilities. Our miRNA-based strategy continues to uncover novel genes closely involved in the oncogenesis of HNSCC.

20.
Bioengineered ; 13(2): 3323-3332, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35048795

RESUMEN

Cervical cancer is a common gynecological malignancy, and miR-133b is an abnormally expressed cervical cancer gene, which suggests that miR-133b may be involved in the occurrence and development of cervical cancer. However, the underlying mechanism is still unclear. miR-133b was overexpressed or silenced in the cervical cancer cell line C33A. Brefeldin A-inhibited guanine nucleotide-exchange protein 1 (ARFGEF1) was combined with overexpression of miR-133b in C33A cells. Cell Counting Kit-8, clone formation, and Transwell assays were performed to determine the influence of miR-133b and ARFGEF1 on clone formation, proliferation, migration, and invasion of C33A cells. The interaction between miR-133b and ARFGEF1 was verified using a luciferase reporter assay. Finally, the mRNA and protein expression of miR-133b and ARFGEF1 in the tumor and adjacent normal tissues of cervical cancer patients was detected by real-time quantitative PCR, Western blotting, and immunohistochemistry. The results indicated that miR-133b up-regulation suppressed the proliferation, invasion, migration, and clone formation abilities of C33A cells (P < 0.05). However, silence of miR-133b promoted the proliferation, invasion, and migration of C33A cells (P < 0.05). Clone formation ability of C33A cells was also elevated by miR-133b deficiency (P < 0.05). Moreover, miR-133b interacted with ARFGEF1 and repressed ARFGEF1 expression in C33A cells (P < 0.05). ARFGEF1 overexpression weakened miR-133b overexpression-mediated inhibition of proliferation, invasion, and migration of C33A cells (P < 0.05). miR-133b expression was decreased, and ARFGEF1 was up-regulated in tumor tissues of cervical cancer patients (P < 0.05). All results revealed that miR-133b suppresses cervical cancer progression by inhibiting proliferation, invasion, and migration of cervical cancer cells via targeting ARFGEF1. Thus, our study determined the mechanism of miR-133b in cervical cancer, and confirmed miR-133b/ARFGEF1 may become a potential therapeutic target for cervical cancer.


Asunto(s)
Movimiento Celular , Proliferación Celular , Factores de Intercambio de Guanina Nucleótido/metabolismo , MicroARNs/metabolismo , Proteínas de Neoplasias/metabolismo , ARN Neoplásico/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Línea Celular Tumoral , Femenino , Factores de Intercambio de Guanina Nucleótido/genética , Humanos , MicroARNs/genética , Invasividad Neoplásica , Proteínas de Neoplasias/genética , ARN Neoplásico/genética , Neoplasias del Cuello Uterino/genética
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