Anti-Warburg Mechanism of Ginsenoside F2 in Human Cervical Cancer Cells via Activation of miR193a-5p and Inhibition of ß-Catenin/c-Myc/Hexokinase 2 Signaling Axis.

Though Ginsenoside F2 (GF2), a protopanaxadiol saponin from Panax ginseng, is known to have an anticancer effect, its underlying mechanism still remains unclear. In our model, the anti-glycolytic mechanism of GF2 was investigated in human cervical cancer cells in association with miR193a-5p and the ß-catenin/c-Myc/Hexokinase 2 (HK2) signaling axis. Here, GF2 exerted significant cytotoxicity and antiproliferation activity, increased sub-G1, and attenuated the expression of pro-Poly (ADPribose) polymerase (pro-PARP) and pro-cysteine aspartyl-specific protease (procaspase3) in HeLa and SiHa cells. Consistently, GF2 attenuated the expression of Wnt, ß-catenin, and c-Myc and their downstream target genes such as HK2, pyruvate kinase isozymes M2 (PKM2), and lactate dehydrogenase A (LDHA), along with a decreased production of glucose and lactate in HeLa and SiHa cells. Moreover, GF2 suppressed ß-catenin and c-Myc stability in the presence and absence of cycloheximide in HeLa cells, respectively. Additionally, the depletion of ß-catenin reduced the expression of c-Myc and HK2 in HeLa cells, while pyruvate treatment reversed the ability of GF2 to inhibit ß-catenin, c-Myc, and PKM2 in GF2-treated HeLa cells. Notably, GF2 upregulated the expression of microRNA139a-5p (miR139a-5p) in HeLa cells. Consistently, the miR139a-5p mimic enhanced the suppression of ß-catenin, c-Myc, and HK2, while the miR193a-5p inhibitor reversed the ability of GF2 to attenuate the expression of ß-catenin, c-Myc, and HK2 in HeLa cells. Overall, these findings suggest that GF2 induces apoptosis via the activation of miR193a-5p and the inhibition of ß-catenin/c-Myc/HK signaling in cervical cancer cells.

Reducing metastasis ability of gastric cancer cell line by targeting MMP16 using miR-193a-5p and 5-FU.

PURPOSE: Co-administration of microRNAs and chemotherapy drugs effectively treats several cancers. The current study sought to investigate the function of matrix metalloproteinase 16 (MMP16) and miR-193a-5p in the pathogenesis of gastric cancer (GC). MATERIALS/METHODS: Sixty-five surgical patients, 15 receiving 5-fluorouracil (5-FU), provided GC and adjacent non-cancerous tissue. Following that, qPCR was used to assess the expression levels of MMP16 and miR-193a-5p in GC cells. The impact of miR-193a-5p and 5-FU administration on MMP16 mRNA expression was evaluated using qRT-PCR and Western blotting. MTT and Scratch tests were also conducted to assess their effects on cell viability and migration. Moreover, a rescue experiment using an MTT assay was performed. Using flow cytometry, the apoptotic rate was calculated. Finally, it was evaluated how MMP16 and miR-193a-5p related to the clinicopathological characteristics of the patients. RESULTS: The current study found that while MMP16 expression increased in GC patients (P â€‹< â€‹0.0001), miR-193a-5p expression significantly decreased (P â€‹< â€‹0.001). MMP16 down-regulation was another effect of miR-193a-5p replacement, particularly when 5-FU was added (P â€‹< â€‹0.01). In addition, this study found that miR-193a-5p, by concentrating on MMP16, decreased the migration of GC cells brought on by MMP16. In GC cell lines, miR-193 and 5-FU induce apoptosis, with the 5-FU being more pronounced when combined with mir-193, according to flow cytometry results. A strong correlation was also found between clinicopathological traits associated with MMP16 and miR-193a-5p. CONCLUSIONS: These findings suggest that miR-193a-5p, in conjunction with 5-FU, down-regulates MMP16 in GC, where it suppresses tumor growth.

[Retracted] Knockdown of SNHG16 suppresses the proliferation and induces the apoptosis of leukemia cells via miR­193a­5p/CDK8.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the colony formation assay data shown in Fig. 7A on p. 1183 were strikingly similar to data appearing in different form in the following article written by different authors at different research institutes that had already been published prior to its date of submission: Lou L, Chen G, Zhong B and Liu F: Lycium barbarum polysaccharide induced apoptosis and inhibited proliferation in infantile hemangioma endothelial cells via down­regulation of PI3K/AKT signaling pathway. Biosci Rep 39: BSR20191182, 2019. In addition, possible anomalies were noted regarding the appearance of the western blots in the paper. Owing to the fact that the contentious data in the above article had already been published prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 46: 1175­1185, 2020; DOI: 10.3892/ijmm.2020.4671].

The role of hsa-miR-193a-5p as an important factor for control of inositol in alopecia areata.

BACKGROUND: MicroRNAs (miRNAs) are small RNA molecules that play a regulatory role in various biological processes by acting as intracellular mediators. They hold great potential as therapeutic agents for targeting human disease pathways; however, there is still much to be uncovered about their mechanism of gene regulation. Alopecia areata (AA) is a commonly occurring inflammatory condition characterized by the infiltration of T cells that specifically target the anagen-stage hair follicle. The limited understanding of its precise cellular mechanism may be the reason behind the scarcity of effective treatments for AA. AIM: The significance and function of hsa-miR-193a-5p as a genetic marker for AA and its potential influence on the advancement of the disease. SUBJECTS AND METHODS: A case-control study comprised 77 individuals diagnosed with AA who were matched with 75 healthy controls. In order to measure the expression of miR-200c-3p in both groups, the real-time PCR technique was utilized. The prediction of suitable genes for hsa-miR-193a-5p, as well as the identification of pathways and gene-gene interactions, were carried out using bioinformatic tools. RESULTS: The levels of hsa-miR-193a-5p expression were notably elevated in AA patients in comparison to healthy controls. Our prediction suggests that the involvement of hsa-miR-193a-5p in the development of AA is significant due to its influence on the inositol phosphorylation pathway and the Phosphatidylinositol signaling system, achieved through its direct impact on the IPPK gene. CONCLUSION: For the first time, our study demonstrates the significant over-expression of a new miRNA, hsa-miR-193a-5p, in the blood of AA patients compared to controls, and highlights its impact on the IPPK gene and the inositol phosphorylation and Phosphatidylinositol signaling pathways, suggesting a potential therapeutic role for hsa-miR-193a-5p in AA.

LncRNA HEIH modulates the proliferation, migration, and invasion of hepatocellular carcinoma cells by regulating the miR-193a-5p/CDK8 axis.

Background: Hepatocellular carcinoma (HCC), a malignant tumor with a high mortality rate, is a serious problem worldwide. This research sought to examine how long non-coding RNA (lncRNA) high expression in hepatocellular carcinoma (HEIH) affects the development and progression of HCC. Methods: The expression of HEIH in HCC patients and HCC cell lines was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, HEIH was knocked down, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide, wound-healing and transwell assays were conducted to evaluate the effects of HEIH on the proliferation, migration, and invasion of the HCC cells, respectively. A xenografted mice model was constructed to investigate the function of HEIH on HCC tumorigenesis in vivo. The interactions among HEIH, microRNA (miR)-193a-5p and cyclin-dependent kinase 8 (CDK8) were also investigated by dual luciferase reporter (DLR) gene and RNA immunoprecipitation (RIP) assays. Results: HEIH was highly expressed in HCC tissues, and was correlated with advanced TNM stage and the absence of vascular invasion. The in vitro experiments showed that silencing HEIH restrained the viability, migration, and invasion of HCC cells, and hampered xenograft tumor growth in vivo. Additionally, HEIH was shown to bind directly to microRNA 193a-5p (miR-193a-5p) and facilitate the expression of the target gene CDK8 in the HCC cells. CDK8 overexpression and miR-193a-5p silencing attenuated the effects of si-HEIH-induced inhibition on the proliferation, migration, and invasion of HCC cells. Conclusions: Silencing HEIH restrained the proliferation, migration, and invasion of HCC cells via the miR-193a-5p/CDK8 axis.

Qingjie Huagong decoction inhibits pancreatic acinar cell pyroptosis by regulating circHipk3/miR-193a-5p/NLRP3 pathway.

BACKGROUND: Safer and more effective drugs are needed for the treatment of acute pancreatitis (AP). Qingjie Huagong decoction (QJHGD) has been applied to treat AP for many years and has shown good clinical effects. However, the potential mechanism has not yet been determined. PURPOSE: To investigate the role and underlying mechanism of the effects of QJHGD on AP both in vitro and in vivo. METHODS: QJHGD was characterized by UHPLC-Q-Orbitrap-MS. The protective effect of QJHDG and the underlying mechanism were investigated in MPC-83 cells in vitro. A caerulein-induced AP model was established to evaluate the protective effect of QJHGD in mice. CCK-8 assays were used to detect cell viability. The contents of inflammatory mediators were determined by ELISA. Expression levels of circRNA, miRNA and mRNA were determined by qRT-PCR. Protein expression was determined using Western blot. Pancreatic tissues were assessed by hematoxylin and eosin staining as well as immunohistochemical and immunofluorescence analyses. Pull-down and luciferase activity assays were performed to determine the regulatory relationships of circHipk3, miR-193a-5p and NLRP3. RESULTS: Our results confirmed that mmu-miR-193a-5p was sponged by mmu-circHipk3, and NLRP3 was a target of miR-193a-5p. In vitro experiments showed that QJHGD enhanced MPC-83 cell viability by regulating circHipk3 sponging mir-193a-5 targeting NLRP3 and inhibiting pyroptosis-related factors. Finally, we showed that QJHGD ameliorated pancreatic tissue injury in AP mice via this pathway. CONCLUSION: This study demonstrate that QJHDG exerted its anti-AP effects via the circHipk3/miR-193a-5p/NLRP3 pathway, revealing a novel mechanism for the therapeutic effect of QJHDG on AP.

LncRNA LINC01569 promotes M2 macrophage polarization to accelerate hypopharyngeal carcinoma progression through the miR-193a-5p/FADS1 signaling axis.

Background: Long non-coding RNA (lncRNA) LINC01569 plays an important role in regulating the tumor microenvironment (TME) and macrophage polarization. However, whether it participates in the progression of hypopharyngeal carcinoma by regulating the TME remains unclear. Methods: An online database was used to analyze clinical data. Macrophage polarization was detected using qRT-PCR and flow cytometry. In vivo experiments were performed using tumor-bearing nude mice. A co-culture system of hypopharyngeal carcinoma cells and macrophages was used to explore the interactions between the two cell types. Results: LINC01569 enhancement was observed in hypopharyngeal carcinoma tumor-associated macrophages (TAMs). In IL4-induced M2 macrophages, the expression of LINC01569 increased, while LINC01569 expression declined significantly in LPS-induced M1 macrophages. SiRNA-mediated downregulation of LINC01569 inhibits IL4-induced M2 macrophage polarization. Using online databases and a dual-luciferase reporter, miR-193a-5p was confirmed as a potential downstream sponge of LINC01569. MiR-193a-5p expression decreased in IL4-mediated M2 macrophages, which was restored by LINC01569 downregulation. Additionally, LINC01569 inhibition-mediated blocking of M2 macrophage polarization was moderately abolished by transfection with the miR-193a-5p inhibitor. Fatty acid desaturase 1 (FADS1) was verified as a downstream target of miR-193a-5p, and LINC01569 downregulation-mediated inhibition of FADS1 was blocked by miR-193a-5p mimics. Importantly, LINC01569 downregulation-mediated decline in M2 macrophage polarization was abolished by miR-193a-5p mimics, which was further reversed by FADS1 knockdown. Implantation of a mixture of FaDu cells and IL4-induced macrophages promoted tumor growth and proliferation, which were abrogated by the knockdown of LINC01569 in macrophages. Using an in co-culture system of FaDu cells and macrophages in vitro, M2 macrophage-regulated cell growth and apoptosis of FaDu cells were found to be mediated by the LINC01569/miR-193a-5p signaling axis. Conclusion: LINC01569 is highly expressed in the TAMs of hypopharyngeal carcinoma. LINC01569 downregulation restrains macrophages from polarizing toward M2 through the miR-193a-5p/FADS1 signaling axis, thereby helping tumor cells escape inherent immune surveillance and promoting the occurrence and development of hypopharyngeal carcinoma.

RelB represses miR-193a-5p expression to promote the phenotypic transformation of vascular smooth muscle cells in aortic aneurysm.

Aortic aneurysm (AA) is a potentially fatal disease with the possibility of rupture, causing high mortality rates with no effective drugs for the treatment of AA. The mechanism of AA, as well as its therapeutic potential to inhibit aneurysm expansion, has been minimally explored. Small non-coding RNA (miRNAs and miRs) is emerging as a new fundamental regulator of gene expression. This study aimed to explore the role and mechanism of miR-193a-5p in abdominal aortic aneurysms (AAA). In AAA vascular tissue and Angiotensin II (Ang II)-treated vascular smooth muscle cells (VSMCs), the expression of miR-193a-5 was determined using real-time quantitative PCR (RT-qPCR). Western blotting was used to detect the effects of miR-193a-5p on PCNA, CCND1, CCNE1, and CXCR4. To detect the effect of miR-193a-5p on the proliferation and migration of VSMCs, CCK-8, and EdU immunostaining, flow cytometry, wound healing, and Transwell Chamber analysis were performed. In vitro results suggest that overexpression of miR-193a-5p inhibited the proliferation and migration of VSMCs, and its inhibition aggravated their proliferation and migration. In VSMCs, miR-193a-5p mediated proliferation by regulating CCNE1 and CCND1 genes and migration by regulating CXCR4. Further, in the Ang II-induced abdominal aorta of mice, the expression of miR-193a-5p was reduced and significantly downregulated in the serum of patients with aortic aneurysm (AA). In vitro studies confirmed that Ang II-induced downregulation of miR-193a-5p in VSMCs by upregulation of the expression of the transcriptional repressor RelB in the promoter region. This study may provide new intervention targets for the prevention and treatment of AA.

Circ_0048856 competes with ABCC1 for miR-193a-5p/miR-98-5p binding sites to promote the cisplatin resistance and tumorigenesis in lung cancer.

Although cisplatin (DDP)-based therapy is the most predominant chemotherapeutic strategy used for lung cancer, drug resistance usually occurs after several cycle use of it. Circular RNAs (circRNAs) are found to be involved in the chemoresistance in lung cancer. Hence, this study aimed to clarify the role and mechanism of circ_0048856 in lung cancer tumorigenesis and DDP resistance. The levels of circ_0048856, miR-193a-5p, miR-98-5p and ABCC1 (ATP Binding Cassette Subfamily C Member 1) were determined by qRT-PCR and western blotting. In vitro assays were conducted by cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine (EDU) assay, flow cytometry and transwell assay, respectively. The binding interaction was verified using dual-luciferase reporter assay and RIP assay. In vivo experiment was performed by the establishment of murine xenograft model. Circ_0048856 was highly expressed in DDP-resistant lung cancer tissues and cells. Functionally, circ_0048856 silencing re-sensitized DDP-resistant lung cancer cells to DDP, as well as suppressed cell growth and invasion in lung cancer in vitro and in vivo. Mechanistically, circ_0048856 acted as the sponge for miR-193a-5p or miR-98-5p, which targeted ABCC1. Furthermore, rescue experiments showed that inhibition of miR-193a-5p or miR-98-5p reversed the effects of circ_0048856 knockdown on lung cancer cells. Besides that, overexpression of miR-193a-5p or miR-98-5p suppressed cell tumorigenesis and reduced DDP resistance in lung cancer, which were attenuated by ABCC1 up-regulation. Circ_0048856 knockdown suppressed tumor growth and reduced DDP resistance in lung cancer by miR-193a-5p/ABCC1 or miR-98-5p/ABCC1 axis, indicating a novel strategy for efficient application of DDP in lung cancer.

MicroRNA-193a-5p Rescues Ischemic Cerebral Injury by Restoring N2-Like Neutrophil Subsets.

Circulating neutrophils are activated shortly after stroke and in turn affect the fate of ischemic brain tissue, and microRNAs (miRNA) participate in regulating neuroinflammation. We probed the role of neutrophilic miRNA in ischemic stroke. miR-193a-5p was decreased in circulating neutrophils of acute ischemic stroke (AIS) patients and healthy controls. In another set of AIS patients treated with recombinant tissue plasminogen activator, higher neutrophilic miR-193a-5p levels were associated with favorable outcomes at 3 months and non-symptomatic intracerebral hemorrhage. An experimental stroke model and human neutrophil-like HL-60 cells were further transfected with agomiR-193a-5p/antagomiR-193a-5p or ubiquitin-conjugating enzyme V2 (UBE2V2)-siRNA prior to model induction for in vivo and in vitro studies. Results of 2,3,5-triphenyl tetrazolium chloride staining and neurological function evaluations at post-experimental stroke showed that intravenous agomiR-193a-5p transfusion protected against ischemic cerebral injury in the acute stage and promoted neurological recovery in the subacute stage. This protective role was suggested to correlate with neutrophil N2 transformation based on the N2-like neutrophil proportions in the bone marrow, peripheral blood, and spleen of the experimental stroke model and the measurement of neutrophil phenotype-associated molecule levels. Mechanistically, analyses indicated that UBE2V2 might be a target of miR-193a-5p. Cerebral injury and neuroinflammation aggravated by miR-193a-5p inhibition were reversed by UBE2V2 silencing. In conclusion, miR-193a-5p protects against cerebral ischemic injury by restoring neutrophil N2 phenotype-associated neuroinflammation suppression, likely, in part, via UBE2V2 induction.

Long Non-coding RNA LINC01224 Promotes the Malignant Behaviors of Triple Negative Breast Cancer Cells via Regulating the miR-193a-5p/NUP210 Axis.

Triple negative breast cancer (TNBC) is a prevalent malignant tumor in women and is characterized by high incidence and mortality. Current evidence has suggested that multiple long noncoding RNAs (lncRNAs) play regulatory roles in TNBC, while the specific mechanism of LINC01224 in TNBC remains unclear. In this study, LINC01224 was highly expressed in TNBC cells. Moreover, LINC01224 downregulation inhibited TNBC cell proliferation, migration, and invasion, and promoted cell apoptosis. Additionally, LINC01224 stabilized NUP210 mRNA through interaction with miR-193a-5p, thereby aggravating the malignant phenotypes of TNBC. Overall, LINC01224 functions as a tumor promoter for TNBC.

Circ_0001667 Promotes Adriamycin Resistance and Malignant Progression via Targeting the miR-193a-5p/Rap2A Molecular Axis in Breast Cancer.

BACKGROUND: The therapeutic effect of adriamycin (ADM) has been limited by chemoresistance in breast cancer (BC). Circular RNAs are involved in resistance regulation by mediating the miRNA/mRNA axis. Circ_0001667 enhanced ADM resistance via the miR-4458/NCOA3 axis in BC. This study was to investigate the other miRNA/mRNA network for circ_0001667. METHODS: The level detection of circ_0001667, microRNA-193a-5p (miR-193a-5p) or Ras-Related Protein 2a (Rap2A) was conducted by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Half inhibitory concentration (IC50) of ADM was detected through cell counting kit-8 (CCK-8) assay. The proliferation analysis was performed by colony formation assay and EdU assay. Flow cytometry was used for assessing apoptosis. Transwell assay was applied for examining cell migration and invasion. The protein detection was carried out by western blot. In vivo assay was performed using xenograft tumor model. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were implemented to validate the target interaction. RESULTS: Circ_0001667 was highly expressed in ADM-resistant BC tissues and cells. Downregulation of circ_0001667 reduced ADM resistance and inhibited proliferation, migration, invasion in ADM-resistant BC cells. Tumor growth was repressed by circ_0001667 knockdown in ADM-resistant xenograft model. Circ_0001667 has induced the sponge effect on miR-193a-5p. The circ_0001667 function was partly achieved by targeting miR-193a-5p. Rap2A expression was positively regulated by circ_0001667 through sponging miR-193a-5p. The miR-193a-5p upregulation restrained chemoresistance and BC progression by the downregulation of Rap2A. CONCLUSION: All results unraveled that circ_0001667 contributed to ADM resistance and tumor development in BC via the miR-193a-5p-mediated Rap2A expression change, providing a novel regulatory mechanism for circ_0001667.

Keloid Patient Plasma-Derived Exosomal hsa_circ_0020792 Promotes Normal Skin Fibroblasts Proliferation, Migration, and Fibrogenesis via Modulating miR-193a-5p and Activating TGF-ß1/Smad2/3 Signaling.

Background: Keloids are fibroproliferative disorders, which seriously affect the quality of life of patients with keloids. Additionally, circRNAs are enriched within exosomes derived from human blood samples, whereas their relationship with keloids remains largely unknown. It has been reported that hsa_circ_0020792 was abnormally upregulated in keloid tissues. However, the role of keloid patient plasma-derived exosomal hsa_circ_0020792 in the formation and development of keloids is not well understood. Methods: Exosomes were isolated from the peripheral blood plasma of the patients with keloids (keloid patient-Exo) and healthy controls (Healthy control-Exo). The hsa_circ_0020792 and miR-193a-5p levels in keloid patient-Exo and healthy control-Exo, as well as in keloid fibroblasts and normal skin fibroblasts (NFs) were evaluated by RT-qPCR. Results: The level of hsa_circ_0020792 was remarkably increased in keloid patient-Exo and keloid fibroblasts compared with that in Healthy control-Exo and NFs, respectively. In addition, keloid patient-Exo obviously enhanced the viability, migration, and extracellular matrix (ECM) synthesis, but reduced the apoptosis of NFs. Moreover, keloid patient-Exo notably promoted the fibrogenesis of NFs, as characterized by enhanced TGF-ß signaling, increased expressions of phosphorylated Smad2/3. However, downregulation of hsa_circ_0020792 markedly reversed the promoting effects of keloid patient-Exo on cell growth, migration, and myofibroblast activation and fibrogenesis. Furthermore, downregulation of hsa_circ_0020792 significantly reduced the viability, migration, and fibrogenesis in NFs, whereas these phenomena were reversed by miR-193a-5p inhibitor. Conclusion: Collectively, keloid patient plasma-derived exosomal hsa_circ_0020792 could promote the proliferation, migration, and fibrogenesis of NFs via modulating miR-193a-5p and activating TGF-ß1/Smad2/3 signaling.

Diagnostic Potential of microRNAs in Extracellular Vesicles Derived from Bronchoalveolar Lavage Fluid for Pneumonia-A Preliminary Report.

Current clinical needs require the development and use of rapid and effective diagnostic indicators to accelerate the identification of pneumonia and the process of microbiological diagnosis. MicroRNAs (miRNAs) in extracellular vesicles (EVs) have become attractive candidates for novel biomarkers to evaluate the presence and progress of many diseases. We assessed their performance as biomarkers of pneumonia. Patients were divided into the pneumonia group (with pneumonia) and the control group (without pneumonia). We identified and compared two upregulated miRNAs in EVs derived from bronchoalveolar lavage fluid (BALF-EVs) between the two groups (PmiR-17-5p = 0.009; PmiR-193a-5p = 0.031). Interestingly, in cell-debris pellets and EVs-free supernatants derived from bronchoalveolar lavage fluid (BALF-cell-debris pellets and BALF-EVs-free supernatants), total plasma, and EVs derived from plasma (plasma-EVs), the expression of miR-17-5p and miR-193a-5p showed no difference between pneumonia group and control group. In vitro experiments revealed that miR-17-5p and miR-193a-5p were strikingly upregulated in EVs derived from macrophages stimulated by lipopolysaccharide. MiR-17-5p (area under the curve, AUC: 0.753) and miR-193a-5p (AUC: 0.692) in BALF-EVs are not inferior to procalcitonin (AUC: 0.685) in the diagnosis of pneumonia. Furthermore, miR-17-5p and miR-193a-5p in BALF-EVs had a significantly higher specificity compared to procalcitonin and could be served as a potential diagnostic marker. MiR-17-5p and miR-193a-5p in EVs may be involved in lung inflammation by influencing the forkhead box O (FoxO) signaling pathway and protein processing in endoplasmic reticulum. This study is one of the few studies which focused on the potential diagnostic role of miRNAs in BALF-EVs for pneumonia and the possibility to use them as new biomarkers for a rapid and early diagnosis.

Integrated Bioinformatics Analysis of Serine Racemase as an Independent Prognostic Biomarker in Endometrial Cancer.

Endometrial cancer (EC) kills about 76,000 women worldwide, with the highest incidence in industrialized countries. Because of the rise in disease mortality and new diagnoses, EC is now a top priority for women's health. Serine racemase (SRR) is thought to play a role in the central nervous system, but its role in cancers, particularly in EC, is largely unknown. The current study starts with a pan-cancer examination of SRR's expression and prognostic value before delving into SRR's potential cancer-suppressing effect in patients with EC. SRR may affect the endometrial tumor immune microenvironment, according to subsequent immune-related analysis. SRR expression is also linked to several genes involved in specific pathways such as ferroptosis, N6-methyladenosine methylation, and DNA damage repair. Finally, we used the expression, correlation, and survival analyses to investigate the upstream potential regulatory non-coding RNAs of SRR. Overall, our findings highlight the prognostic significance of SRR in patients with EC, and we can formulate a reasonable hypothesis that SRR influences metabolism and obstructs key carcinogenic processes in EC.

MiR-193a-5p serves as an inhibitor in ovarian cancer cells through RAB11A.

Ovarian cancer is often not diagnosed until it is in advanced stages and its cure rate is relatively low. Thus, this investigation is concerned about the pathogenesis of this cancer. Differential expression analysis was undertaken on messenger RNA (mRNA) and microRNA (miRNA) data of ovarian cancer in Gene Expression Profiling Interactive Analysis and Gene Expression Omnibus databases. RAB11A mRNA and miR-193a-5p expression levels were tested by quantitative polymerase chain reaction. The targeting relationship between RAB11A and miR-193a-5p was verified by dual-luciferase assay. Cell behaviors of ovarian cancer were tested by Cell-Counting-Kit-8, colony formation and transwell assays. Expression of RAB11A protein and the proteins associated with Wnt/ß-catenin was tested by western blot. RAB11A high expression and miR-193a-5p low expression were found in ovarian cancer cells. RAB11A was targeted by miR-193a-5p. Cellular function experiments proved that RAB11A facilitated Wnt/ß-catenin signaling activation and deteriorated ovarian cancer progression. Rescue experiments exhibited two results: miR-193a-5p hindered proliferation, migration and invasion of ovarian cancer cells, and this suppression was counteracted by overexpression of RAB11A and miR-193a-5p. Furthermore, miR-193a-5p repressed RAB11A-mediated Wnt/ß-catenin activation. Altogether, miR-193a-5p served as a modulator in ovarian cancer cells via targeting RAB11A.

LncRNA SNHG11 accelerates the progression of lung adenocarcinoma via activating Notch pathways.

BACKGROUND: Numerous researches have emphasized that long non-coding RNAs (lncRNAs) have a close association with the biological process in multiple cancers including lung adenocarcinoma (LUAD). Nevertheless, the detailed function and potential mechanism of Small nucleolar RNA Host Gene 11 (SNHG11) in LUAD keep unknown. METHODS: Quantitative reverse transcription polymerase chain reaction (RT-qPCR) tested SNHG11, miR-193a-5p and notch receptor 3 (Notch3) expression. Functional assays tested the function of SNHG11 in LUAD cells. The relationship among SNHG11, miR-193a-5p and Notch3 was verified by mechanism assays. In vivo assays were implemented to reveal the role of SNHG11 in LUAD tumor growth. RESULTS: SNHG11 was evidently high expressed in LUAD cells in comparison to normal lung epithelial cells. Moreover, down-regulation of SNHG11 hindered viability, proliferation and migration of LUAD cells as well as tumor growth. As for the mechanisms, SNHG11 activated Notch pathway via regulating Notch3. In addition, SNHG11 competitively bound with miR-193a-5p to up-regulate Notch3. The last rescue assays displayed that SNHG11 affecting LUAD cell malignant behaviors via regulating miR-193a-5p/SNHG11. CONCLUSION: SNHG11 regulated miR-193a-5p/Notch3 axis to activate Notch pathway, consequently facilitating the proliferation and migration in LUAD.

LINC01224 facilitates the proliferation and inhibits the radiosensitivity of melanoma cells through the miR-193a-5p/NR1D2 axis.

Melanoma is a skin cancer characterized by early metastasis and high mortality. Radiotherapy is a common treatment for melanoma in patients. Long noncoding RNAs play pivotal roles in regulating the radiosensitivity of many tumors, including melanomas. In this study, the role of LINC01224 in the radiosensitivity of melanoma cells was explored. The expression of LINC01224 in melanoma was examined by reverse transcription-quantitative polymerase chain reaction, and the results showed that LINC01224 was upregulated in melanoma tissues and cells. The effects of LINC01224 on cell proliferation and apoptosis in melanoma were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT), colony formation, and flow cytometry assays. The effects of LINC01224 on the radiosensitivity of melanoma were analyzed by colony formation assay. The results implied that LINC01224 knockdown inhibited cell viability and proliferation but enhanced cell apoptosis and radiosensitivity. Luciferase reporter and RNA pull-down assays were performed to evaluate the relationships between LINC01224 and miR-193a-5p or miR-193a-5p and nuclear receptor subfamily 1 group D member 2 (NR1D2). We found that LINC01224 binds to miR-193a-5p, which directly targets NR1D2. In addition, we discovered that LINC01224 upregulated NR1D2 expression by sponging miR-193a-5p in melanoma cells. Overall, the data collected in this study suggest that LINC01224 exerts oncogenic effects in melanoma via the miR-193a-5p/NR1D2 axis.

lncRNA SNHG11 promotes the malignant biological behaviors of NSCLC A549 cells by adsorbing miR-193a-5p / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the effect of lncRNA SNHG11 on the proliferation, invasion and migration of non-small cell lung cancer (NSCLC) A549 cells and its possible mechanisms. Methods: qPCR was used to detect the levels of lncRNA SNHG11 and miR-193a-5p in human embryonic lung cells (HEL-1) and lung cancer cells (A549, H1299, and HCC827). A549 cells were transfected with SNHG11 small interfering RNA (si-SNHG11), miR-193a mimic or miR-193a inhibitor. The proliferation of A549 cells was detected by CCK-8 assay, migration and invasion of A549 cells were detected by Wound healing and Transwell assay, the protein expression of Ki67 and Cyclin D1 was determined by Western blot, and the targeting relationship between lncRNA SNHG11 and miR-193a-5p was verified by Dual-luciferase reporter experiment. Results: Compared with HEL-1 cells, the expression level of lncRNA SNHG11 was significantly increased while the expression of miR-193a-5p was decreased in lung cancer A549, H1299 and HCC827 cells (all P<0.05). Silencing lncRNA SNHG11 inhibited the proliferation, migration and invasion of A549 cells and reduced the protein expression of Ki67 and Cyclin D1 (all P<0.05). Over-expression of miR-193a-5p inhibited the proliferation, migration and invasion of A549 cells (all P<0.05). lncRNA SNHG11 could targetedly adsorb miR-193a-5p. miR-139a-5p inhibition could partially reverse the effect of silencing lncRNA SNHG11 on the proliferation, invasion and migration of A549 cells (all P<0.05). Conclusion: lncRNA SNHG11 promotes the proliferation, invasion and migration of NSCLC cells by adsorbing miR-193a-5p.

The miR-193a-5p/NCX2/AKT axis promotes invasion and metastasis of osteosarcoma.

MiR-193a-5p has been observed to have oncogenic or tumor suppressive functions in different kinds of cancers, but its role and molecular mechanism in osteosarcoma are elusive. Na+/Ca2+ exchangers (NCX1, NCX2 and NCX3) normally extrude Ca2+ from the cell, and deregulation of the intracellular Ca2+ homeostasis is related to several kinds of diseases, including cancer. The present study demonstrated that miR-193a-5p was upregulated in osteosarcoma tissues compared with the corresponding adjacent noncancerous tissues, and promoted colony formation, migration, invasion and epithelial-mesenchymal transition (EMT) in osteosarcoma cells (SaOS-2 and U-2OS), as well as metastasis in a murine xenograft model. Tandem mass tag-based quantitative proteomics analysis identified NCX2 as a potential target of miR-193a-5p. Luciferase activity assays and Western blotting further confirmed that miR-193a-5p recognized the 3'-untranslated region of NCX2 mRNA, and negatively regulated NCX2 expression. NCX2 was downregulated in osteosarcoma tissues, and its expression was negatively correlated with miR-193a-5p levels. Ectopic expression of NCX2 in osteosarcoma cells could reverse the oncogenicity of miR-193a-5p, indicating that miR-193a-5p exerted its effects by targeting NCX2. Further study demonstrated that NCX2 suppresses Ca2+-dependent Akt phosphorylation by decreasing intracellular Ca2+ concentration, and then inhibited EMT process. Treatment with the antagomir against miR-193a-5p sensitized osteosarcoma to the Akt inhibitor afuresertib in a murine xenograft model. In conclusion, a miR-193a-5p/NCX2/AKT signaling axis contributes to the progression of osteosarcoma, which may provide a new therapeutic target for osteosarcoma treatment.