SHP2 mediates the ROS/JNK/NFAT4 signaling pathway in gastric cancer cells prompting lncRNA SNHG18 to drive gastric cancer growth and metastasis via CAR-T cells.

OBJECTIVE: In gastric cancer cells, the influence of CAR T cells can be produced in the process of inhibiting the progression of gastric cancer, and the role of tyrosine phosphatase SHP2 can be explored in this study, along with its molecular mechanisms. METHODS: The research utilized subcutaneous tumor models in nude mice to assess gastric cancer progression. Protein expression was detected using Western blotting, while Q-PCR examined the expression levels of lncRNA SNHG18 and miR-211-5p in MGC-803 cells. The relationship between miR-211-5p and lncRNA SNHG18 can be analyzed by dual luciferase reporter genes. The migratory ability of MGC-803 cells was determined through wound healing and transwell experiments, and cell proliferation was evaluated using a CCK-8 assay. RESULTS: SHP2 was found to inhibit the cytotoxic effects of CAR-T cells on MGC-803 cells, and it suppressed the expression of proteins related to the ROS/JNK/NFAT4 signaling pathway in MGC-803 cells and the miR-211-5p/BRD4 axis in CAR-T cells. In addition, the proliferation, invasion and migration of MGC-803 cells were promoted, and the expression of miR-211-5p could be inhibited specifically by ncRNA SNHG18, as shown below:SHP2 in gastric cancer cells mediates the ROS/JNK/NFAT4 signaling pathway and induces lncRNA SNHG18, which, through the miR-211-5p/BRD4 axis in CAR-T cells, promotes gastric cancer growth and metastasis.

Association between miR-202, miR-211, and miR-1238 gene polymorphisms and risk of vitiligo.

Vitiligo, as a common pigment defect in the skin, hair, and mucous membranes, results from the destruction of melanocytes. Recent investigations have shown that miRNA dysregulation contributes in the pathogenesis of vitiligo. Therefore, in this research, our aim is to explore the relationship between miR-202 rs12355840, miR-211 rs8039189, and miR-1238 rs12973308 polymorphisms and susceptibility to vitiligo. A total number of 136 vitiligo patients and 129 healthy individuals as a control group were included in this research. The salting out approach was implemented to extraction genomic DNA. The genetic polymorphisms of miR-202 rs12355840, miR-211 rs8039189, and miR-1238 rs12973308 were determined using PCR-RFLP approach. The findings revealed that miR-202 rs12355840 polymorphism under codominant (CT and TT genotypes), dominant, recessive, overdominant, and also allelic models is correlated with increased risk of vitiligo. In addition, codominant, dominant, overdominant, as well as allelic models of miR-211 rs8039189 polymorphism decrease risk of vitiligo. No significant relationship was observed between the miR-1238 rs12973308 polymorphism and susceptibility to vitiligo. The miR-211 rs8039189 polymorphism may serve a protective effect on vitiligo development and miR-202 rs12355840 polymorphism may act as a risk factor for vitiligo susceptibility.

Downregulation of miR-211 expression in the blood plasma of infertile men compared to the fertile controls.

OBJECTIVES: Infertility is inability to conceive after 12 months of regular unprotected sex. MiRNA expression changes can serve as potential biomarkers for infertility in males due to impaired spermatogenesis. This research was conducted to measure the expression level of miR-211 in plasma samples as a factor identifying infertility in comparison with the control group. METHODS: In this study, blood plasma were taken from the infertile men (n = 103) nonobstructive azoospermia (NOA) or severe oligozoospermia (SO) and the control group (n = 121). The expression of circulating miR-211 in plasma was assessed by qRT-PCR. A relative quantification strategy was adopted using the 2-ΔΔCT method to calculate the target miR-211 expression level in both study groups. RESULTS: Plasma miR-211 levels were significantly lower in infertile men compared to the control group (0.544 ± 0.028 and 1.203 ± 0.035, respectively, p < 0.001). Pearson's correlation analysis showed that miR-211 expression level has a positive and significant correlation with sperm parameters, including sperm concentration, sperm total motility, progressive motility, and normal morphology (p < 0.001). CONCLUSIONS: Decreased expression of miR-211 in blood plasma seems to be associated with male infertility. This experiment showed that miR-211 can be considered as a biomarker for evaluation, diagnosis, and confirmation of the results of semen analysis in male infertility.

Gut-Derived Exosomes Mediate the Microbiota Dysbiosis-Induced Spermatogenesis Impairment by Targeting Meioc in Mice.

Diseases like obesity and intestinal inflammation diseases are accompanied by dysbiosis of the gut microbiota (DSGM), which leads to various complications, including systemic metabolic disorders. DSGM reportedly impairs the fertility of male mice; however, the regulatory mechanism is unclear. Exosomes are molecular mediators of intercellular communication, but the regulation of spermatogenesis by non-reproductive tissue-originated exosomes remains unknown. The present study shows that DSGM altered the miRNA expression profile of mouse circulating exosomes and impaired spermatogenesis. Moreover, the single-cell sequencing results indicate that circulating exosomes from mice with DSGM impaired spermatogenesis, while circulating exosomes from wild mice improved spermatogenesis by promoting meiosis. Further study demonstrates that DSGM leads to abnormal upregulation of miR-211-5p in gut-derived circulating exosomes, which inhibited the expression of meiosis-specific with coiled-coil domain (Meioc) in the testes and impaired spermatogenesis by disturbing meiosis process. In summary, this study defines the important role of gut-derived exosomes in connecting the "gut-testis" axis.

Astragaloside IV restrains pulmonary fibrosis progression via the circ_0008898/miR-211-5p/HMGB1 axis.

Pulmonary Fibrosis (PF) is a fatal lung disease with complicated pathogenesis. Astragaloside IV (ASV) has been discovered to alleviate PF progression, and the potential molecular mechanism of ASV in the development of PF need to be further clarified. Bleomycin (BLM) was used to construct PF in vivo model. Expression levels of circ_0008898, miR-211-5p, high mobility group protein B1 (HMGB1), alpha smooth muscle Actin (α-SMA) and Collagen I were examined by Quantitative real time polymerase chain reaction (qRT-PCR) and western blot. Cell survival was analyzed using Cell Counting Kit-8 (CCK-8) and EdU (5-ethynyl-2'-deoxyuridine) assay. The invasion abilities were investigated by transwell assay. The levels of inflammatory factors were tested via using Enzyme-linked immunosorbent assay (ELISA). The relationship between circ_0008898 or HMGB1 and miR-211-5p was identified by dual-luciferase reporter assay. The results showed that ASV attenuated BLM-induced pulmonary fibrosis in vivo. In vitro study, ASV alleviated TGF-ß1-induced fibrogenesis in HFL1 cells. Circ_0008898 was increased in TGF-ß1-induced HFL1 cells. ASV-induced impacts were abrogated by circ_0008898 overexpression in TGF-ß1-induced HFL1 cells. Mechanistically, circ_0008898 competitively bound to miR-211-5p to increase the expression of its target HMGB1. MiR-211-5p deficiency rescued ASV-mediated effects in TGF-ß1-induced HFL1 cells. In addition, HMGB1 overexpression partially overturned circ_0008898 interference-induced impacts in HFL1 cells upon TGF-ß1 treatment. In conclusion, our work manifested that ASV hindered PF process by mediating the circ_0008898/miR-211-5p/HMGB1 network.

Small Extracellular Vesicles Released from miR-211-5p-Overexpressed Bone Marrow Mesenchymal Stem Cells Ameliorate Spinal Cord Injuries in Rats.

Spinal cord injury (SCI) has become one of the common and serious diseases affecting patients' motor functions. The small extracellular vesicles secreted by bone marrow mesenchymal stem cells (BMSCs) have shown a promising prospect for the treatment of neurological diseases. BMSCs were collected from rat bones. Osteogenic and adipogenic differentiation of BMSCs was further determined. Small extracellular vesicles were obtained by high-speed centrifugation. Dual-luciferase reporter assay was performed to demonstrate the targeting of miR-211-5p to the cyclooxygenase 2 (COX2) mRNA. qRT-PCR and Western blot assay were used for the detection of the mRNA and protein expression. ELISA was performed to estimate the levels of proinflammatory factors in spinal cord tissues. Our results showed that miR-211-5p targeted COX2 mRNA and regulated the protein expression of COX2 in BMSCs. Extracellular vesicles released from miR-211-5p-overexpressed BMSCs ameliorated SCI-induced motor dysfunction and motor evoked potential impairments. Extracellular vesicles released from miR-211-5p-overexpressed BMSCs ameliorated SCI-induced COX2 expression and related inflammatory responses. In conclusion, small extracellular vesicles released from miR-211-5p-overexpressed BMSCs ameliorate spinal cord injuries in rats.

MicroRNA 211-5p inhibits cancer cell proliferation and migration in pancreatic cancer by targeting BMP2.

MicroRNAs (miRNAs) are essential to the tumour growth and metastasis of several cancers. However, the implied functions of miR-211-5p in pancreatic cancer (PC) remains poorly known. In the present study, we discovered that miR-211-5p was a significantly downregulated miRNA in PC tissues compared to adjacent non-tumour tissues. Moreover, we revealed that miR-211-5p overexpression suppressed the proliferation and metastasis of PC cells. Mechanistically, miR-211-5p directly bond to 3'UTR of bone morphogenetic protein-2 (BMP2) and negatively regulated its expression. Rescue experiments showed that the biological function of miR-211-5p was reversed by BMP-2 overexpression in PC cells. Clinical data indicated that BMP2 expression was negatively correlated with miR-211-5p levels in PC patients. Our study provided evidence that miR-211-5p served as a significant suppressor in PC, provided potential targets for prognosis and treatment of patients with PC.

CircUSP10 promotes liver cancer progression by regulating miR-211-5p/TCF12/EMT signaling pathway.

There is no precise diagnosis or prognosis for liver cancer (LC) using a single biomarker. Circular RNAs (circRNAs) contribute to the pathogenesis of different cancers, but their role in LC is not entirely understood. In this study, circUSP10, an aberrantly expressed circRNA in LC, was screened using the Gene Expression Omnibus database, and its tissue-specific expression was verified using qRT-PCR. In vitro, functional assays and nude mouse tumorigenesis models were used to investigate circUSP10 role in LC. RNA immunoprecipitation and dual-luciferase reporter assays were performed to study the mechanistic relationship between circUSP10, miR-211-5p, and transcription factor 12 (TCF12). We found that circUSP10 expression was upregulated in LC tissues and cells. CircUSP10 expression was linked to tumor size and tumor node metastasis stage and negatively correlated with LC prognosis. In vitro assays confirmed circUSP10-mediated proliferation, migration, and invasion of LC cells and their association with the epithelial-mesenchymal transition (EMT) pathway. Mechanistically, circUSP10 adsorbed miR-211-5p, which regulated TCF12 and promoted tumorigenesis via the EMT signaling pathway. Therefore, our results suggest that circUSP10 may promote LC progression by modulating the miR-211-5p/TCF12/EMT signaling cascade and may serve as a potential biomarker for LC diagnosis and prognosis.

Critical Considerations for Investigating MicroRNAs during Tumorigenesis: A Case Study in Conceptual and Contextual Nuances of miR-211-5p in Melanoma.

MicroRNAs are non-coding RNAs fundamental to metazoan development and disease. Although the aberrant regulation of microRNAs during mammalian tumorigenesis is well established, investigations into the contributions of individual microRNAs are wrought with conflicting observations. The underlying cause of these inconsistencies is often attributed to context-specific functions of microRNAs. We propose that consideration of both context-specific factors, as well as underappreciated fundamental concepts of microRNA biology, will permit a more harmonious interpretation of ostensibly diverging data. We discuss the theory that the biological function of microRNAs is to confer robustness to specific cell states. Through this lens, we then consider the role of miR-211-5p in melanoma progression. Using literature review and meta-analyses, we demonstrate how a deep understating of domain-specific contexts is critical for moving toward a concordant understanding of miR-211-5p and other microRNAs in cancer biology.

miR-211-5p targeting MMP9 regulates the expressions of AQP4 in traumatic brain injury.

OBJECTIVE: The abnormal expression of matrix metalloproteinase 9 (MMP9) and Aquaporin 4 (AQP4) closely associates with the traumatic brain injury (TBI) development. METHODS: Here, we investigated the relationship between miR-211-5p and MMP9/AQP4 axis in TBI patients and astrocyte cells. Demographics, clinical features, and cerebrospinal fluid (CSF) samples were collected from traumatic brain injury (TBI) patients (n = 96) and controls (n = 30) for pathological and gene expression analyses. Luciferase activity assay and gene expression analyses were performed to dissect the regulatory mechanism of miR-211-5p on MMP9/AQP4 in human astrocyte cells. RESULTS: miR-211-5p mRNA was significantly decreased in the CSF of TBI patients, which positively correlated with the expression of both MMP9 and AQP4. miR-211-5p could target MMP9 directly in SVG P12 cells. Overexpression of miR-211-5p decreased the expression of MMP9, on the contrary, knockdown miR-211-5p through inhibitors increased the expression of both MMP9 and AQP4. CONCLUSION: miR-211-5p inhibits the MMP9/AQP4 axis in human astrocyte cells, which represents a promising approach for the TBI treatment.

Melatonin promotes the development of the secondary hair follicles by regulating circMPP5.

BACKGROUND: The quality and yield of cashmere fibre are closely related to the differentiation and development of secondary hair follicles in the skin of cashmere goats. The higher the density of secondary hair follicles, the higher the quality and yield of cashmere from the fleece. Development of secondary hair follicles commences in the embryonic stage of life and is completed 6 months after birth. Preliminary experimental results from our laboratory showed that melatonin (MT) treatment of goat kids after their birth could increase the density of secondary hair follicles and, thus, improve the subsequent yield and quality of cashmere. These changes in the secondary hair follicles resulted from increases in levels of antioxidant and expression of anti-apoptotic protein, and from a reduction in apoptosis. The present study was conducted to explore the molecular mechanism of MT-induced secondary hair follicle differentiation and development by using whole-genome analysis. RESULTS: MT had no adverse effect on the growth performance of cashmere kids but significantly improved the character of the secondary hair follicles and the quality of cashmere, and this dominant effect continued to the second year. Melatonin promotes the proliferation of secondary hair follicle cells at an early age. The formation of secondary hair follicles in the MT group was earlier than that in the control group in the second year. The genome-wide data results involved KEGG analysis of 1044 DEmRNAs, 91 DElncRNAs, 1054 DEcircRNAs, and 61 DEmiRNAs which revealed that the mitogen-activated protein kinase (MAPK) signaling pathway is involved in the development of secondary hair follicles, with key genes (FGF2, FGF21, FGFR3, MAPK3 (ERK1)) being up-regulated and expressed. We also found that the circMPP5 could sponged miR-211 and regulate the expression of MAPK3. CONCLUSIONS: We conclude that MT achieves its effects by regulating the MAPK pathway through the circMPP5 sponged the miR-211, regulating the expression of MAPK3, to induce the differentiation and proliferation of secondary hair follicle cells. In addition there is up-regulation of expression of the anti-apoptotic protein causing reduced apoptosis of hair follicle cells. Collectively, these events increase the numbers of secondary hair follicles, thus improving the production of cashmere from these goats.

CircRNA Circ_0000118 Regulates Malignancy of Cervical Cancer Cells by Regulating miR-211-5p/miR-377-3p/AKT2 Axis.

CircRNAs are implicated in the development of several cancers. Nevertheless, the involvement of circ_0000118 in the development of cervical cancer (CC) remains unclear. Circ_0000118 levels in tumor tissues and cells were examined by qRT-PCR. The function of circ_0000118 in regulating the malignancy of CC cells was investigated using functional assays, including CCK-8, colony formation, transwell, and tube formation experiments. The functional interaction between circ_0000118 and microRNAs were validated by dual-luciferase activity assay and RNA precipitation experiments. In vivo mouse model was employed to assess the effect of circ_0000118 in the tumorigenesis of CC cells. Circ_0000118 was overexpressed in CC cells and tissues. Loss-of-function experiments demonstrated that circ_0000118 knockdown impaired the proliferation and tumor sphere formation, as well as the angiogenic potential of CC cells. RNA interaction experiments confirmed that circ_0000118 sponged miR-211-5p and miR-377-3p. AKT2 was found to be a target gene negatively modulated by miR-211-5p and miR-377-3p. AKT2 overexpression rescued the inhibition of circ_0000118 downregulation on CC cells. Our study suggested that circ_0000118 functions as an oncogenic factor in progression of CC by maintaining AKT2 level through targeting miR-211-5p and miR-377-3p as a ceRNA (competitive endogenous RNA), which provides novel therapeutic target in the management of CC.

Long noncoding RNA SNHG4 promotes the malignant progression of hepatocellular carcinoma through the miR-211-5p/CREB5 axis.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is one of the main death-leading malignant tumors which deserve in-depth explorations to uncover the underlying molecular mechanisms. Plenty of proofs have revealed that long noncoding RNAs (lncRNAs) participate in malignancy and progression of HCC. Nevertheless, the definite role of lncRNA-SNHG4 in HCC remains vague. METHODS: To figure out the role of SNHG4 in HCC, the bioinformatics analysis and functional assays and in vivo assay were performed. RESULTS: Our findings demonstrated that the data from The Cancer Genome Atlas (TCGA) displayed that the higher expression of lncRNA SNHG4 was detected in HCC tissues, which predicted the poor prognosis. The upregulation of SNHG4 was positively associated with worse clinicopathological characteristics. The functional experiments were performed to identify the role of SNHG4 in HCC. We found that SNHG4 enhanced the proliferative, migratory and invasive capacities of HCC cell line, and facilitated the tumor growth in vivo. A series of follow-up studies have shown that SNHG4 promoted the progression and malignancy of HCC through upregulating CREB5 via sponging miR-211-5p. CONCLUSION: Collectively, the above findings suggest that SNHG4 promotes HCC malignancy through the SNHG4/miR-211-5p/CREB5 axis, providing potential therapeutic targets and prognostic factors for HCC. Highlights SNHG4 is overexpressed in HCC and correlated with the poor clinical characteristics SNHG4 promotes the malignant progression of HCC by reducing miR-211-5p expression MiR-211-5p inhibits CREB5 expression in HCC The oncogenic effect of SNHG4 in HCC can be reversed by CREB5 silencing.

SIRT1 targeted by miR-211-5p regulated proliferation and apoptosis of Dex-treated growth plate chondrocytes via mediating SOX2.

Dexamethasone (Dex) is reported to cause bone growth retardation in children, which is associated with the increased apoptosis and decreased proliferation of growth plate chondrocytes. Sirtuin 1 (SIRT1) plays an important role in chondrocyte function and homeostasis. Thus, we further explored the regulatory mechanism of SIRT1 in Dex-induced growth plate chondrocyte dysfunction. SIRT1 expression was detected in Dex-treated growth plate chondrocytes using RT-qPCR and western blot assay. The modulation of SIRT1 on SOX2 expression was evaluated. Besides, we identified that SIRT1 was targeted by miR-211-5p using TargetScan and RNA pull-down assay. A loss-of-function assay was performed to evaluate the effects of miR-211-5p on Dex-induced growth plate chondrocyte dysfunction in vitro and in vivo. We found that SIRT1 was downregulated in Dex-treated growth plate chondrocytes. The expression of SOX2 was upregulated by overexpression SIRT1. Meanwhile, downregulation of SOX2 weakened the positive function of SIRT1 overexpression on Dex-induced growth plate chondrocytes dysfunction. Subsequently, we confirmed that SIRT1 was targeted by miR-211-5p. MiR-211-5p inhibitor increased the expression levels of SIRT1 and SOX2, and restored the Dex-treated growth plate chondrocyte function. Animal assays further demonstrated that the effects of miR-211-5p on the growth plate chondrogenesis. In conclusion, our data suggest that SIRT1 exerts a protective effect on growth plate chondrocyte under Dex stimulation. MiR-211-5p/SIRT1/SOX2 axis regulates the process of Dex-inhibited growth plate chondrogenesis.

MiR-211 plays a dual role in cancer development: From tumor suppressor to tumor enhancer.

Cancer is a general term for more than 100 unique malignancies in different organs of the body. Each cancer type and subtype has its own unique genetic, epigenetic, and cellular factors accountable for malignant progression and metastasis. Small non-coding RNAs called miRNAs target mRNAs and play a vital part in the pathogenesis of human diseases, specifically cancer. Recent investigations provided knowledge of the deregulation of miR-211 in various cancer types and disclosed that miR-211 has an oncogenic or tumor-suppressive impact on tumourigenesis and cancer development. Moreover, recent discoveries which clarify the essential functions of miR-211 might provide proof for its prognosis, diagnostic and therapeutic impact on cancer. Thereby, this review will discuss recent findings regarding miR-211 expression level, target genes, and mechanisms in different cancers. In addition, the most recent results that propose miR-211 usefulness as a noninvasive biomarker and therapeutic factor for the diagnosis and treatment of cancer will be explained.

Has_circ_0008285/miR-211-5p/SIRT-1 Axis Suppress Ovarian Cancer Cells Progression.

The significant functional role of circular RNAs (circRNAs) in the progression of malignant tumors, including ovarian cancer, has been shown in various studies. In this study, we aimed to investigate the abnormal expression of hsa_circ_0008285 and its role in ovarian cancer pathogenesis. Quantitative real time polymerase chain reaction (qRT-PCR) and Western blot methods were used to detect the expression of hsa_circ_0008285 and some target genes in ovarian cancer tissues and related cell lines. To determine the functional roles of hsa_circ_0008285 in ovarian cancer, cell proliferation, apoptosis, and cell invasion assays were performed. Bioinformatics (Target scan, circ intractome) and luciferase reporter analyses were used to predict target genes. Results: In the present study, we first found that hsa_circ_0008285 was up regulated in ovarian cancer tissues and related cell lines. Bioinformatics, experimental data, and luciferase reporter analysis data showed miR-211-5p is a direct target of hsa_circ_0008285, while SIRT-1 is a direct target of miR-211-5p. Overexpression of hsa_circ_0008285 in cancer cells increased the expression of SIRT-1 and progression of cancer cells. Based on these results, inhibition of hsa_circ_0008285 expression could cause upregulation of miR-211-5p and down regulation of SIRT-1 and inhibited the proliferation and invasion of ovarian cancer cells. Conclusion: The results of the present study revealed that hsa_circ_0008285 suppressed ovarian cancer progression by regulating miR-211-5p expression to inhibit SIRT-1 expression.

MicroRNA-211-5p as a Biomarker in Early Detection of Uremic Vascular Calcification among Patients with End-Stage Renal Disease.

BACKGROUND: Vascular calcification (VC) is a serious pathological manifestation of vascular terminals and is an important pathological basis of cardiovascular diseases in patients with end-stage renal disease (ESRD). This study explored the clinical value of serum microRNA-211-5p (miR-211-5p) in VC in patients with ESRD, this study was designed. METHODS: The relative expression of miR-211-5p in the serum of the calcified group and the non-calcified group was quantified by quantitative reverse transcription polymerase chain reaction. The clinical biochemical indexes and the expression differences in miR-211-5p expression in the serum of groups were compared by two independent samples t-test or nonparametric test or one-way analysis of variance test. The receiver operating characteristic (ROC), Kaplan-Meier, and Cox regression analysis were carried out to analyze the predictive value of serum miR-211-5p in patients with ESRD. RESULTS: The relative quantification of serum miR-211-5p was lessened in calcified group and gradually decreased with the progression of VC. Serum miR-211-5p had a high diagnostic accuracy in the diagnosis of VC progression in ESRD patients. Kaplan-Meier and Cox regression methods revealed that miR-211-5p might be an independent biomarker for prognosis of ESRD patients. CONCLUSIONS: MiR-211-5p is a potential diagnostic and prognostic marker of VC in patients with ESRD.

MicroRNA-211-5p Overexpression Effect on Endoplasmic Reticulum Stress and Apoptotic Genes in Fibroblast-like Synoviocytes of Rheumatoid Arthritis.

Fibroblast-like synoviocytes (FLSs) play a major role in the pathogenesis of rheumatoid arthritis (RA). Endoplasmic reticulum (ER) stress and dysregulation of unfolded protein response are involved in the resistance to apoptosis of FLSs in RA (RA-FLSs). MicroRNA (MiR)-211 plays an important role in controlling ER stress and apoptotic genes in a PKR-like ER kinase (PERK)-activating transcription factor 4 (ATF4)-dependent manner. We investigated the effect of miR-211-5p overexpression on ER stress and apoptotic genes in RA-FLSs. FLSs were isolated from synovial tissues of trauma (n=10) and RA (n=10) patients. MiR-211-5p and mRNA expression of the selected genes involved in the PERK pathway and apoptosis regulation were measured in RA, trauma, and thapsigargin (Tg)-treated RA-FLSs. Afterward, Tg-treated RA-FLSs following miR-211-5p overexpression were evaluated for miR-211-5p and mRNA levels of the study genes. The expression of miR-211-5p, PERK, BAX, and BCL2 showed no differences between RA and trauma. However, the expression of ATF4 and BCL-XL showed a significant increase in trauma. In addition, the levels of C/EBP homologous protein (CHOP) and MCL1 indicated a significant increase in RA-FLSs. Tg treatment significantly increased the expression of PERK, ATF4, and CHOP in RA-FLSs with no effect on miR-211-5p, BAX, BCL2, BCL-XL, and MCL1. Furthermore, Tg treatment following miR-211-5p overexpression in RA-FLSs showed a significant increase in levels of miR-211-5p with no changes in apoptotic genes. MiR-211-5p overexpression in stimulated RA-FLSs did not alter the levels of selected genes involved in apoptosis regulation. However, more investigations are necessary to determine the ER stress role in apoptosis regulation in RA-FLSs.

MicroRNA-211-5p as a Biomarker in Early Detection of Uremic Vascular Calcification among Patients with End Stage Renal Disease

Background: Vascular calcification (VC) is a serious pathological manifestation of vascular terminals and is an important pathological basis of cardiovascular diseases in patients with end-stage renal disease (ESRD). This study explored the clinical value of serum microRNA-211-5p (miR-211-5p) in VC in patients with ESRD, this study was designed. Methods: The relative expression of miR-211-5p in the serum of the calcified group and the non-calcified group was quantified by quantitative reverse transcription polymerase chain reaction. The clinical biochemical indexes and the expression differences in miR-211-5p expression in the serum of groups were compared by two independent samples t-test or nonparametric test or one-way analysis of variance test. The receiver operating characteristic (ROC), Kaplan-Meier, and Cox regression analysis were carried out to analyze the predictive value of serum miR-211-5p in patients with ESRD. Results: The relative quantification of serum miR-211-5p was lessened in calcified group and gradually decreased with the progression of VC. Serum miR-211-5p had a high diagnostic accuracy in the diagnosis of VC progression in ESRD patients. Kaplan-Meier and Cox regression methods revealed that miR-211-5p might be an independent biomarker for prognosis of ESRD patients Conclusions: MiR-211-5p is a potential diagnostic and prognostic marker of VC in patients with ESRD (AU)