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Objective To analyze the relationship between expression levels of long non-coding RNA (LncRNA) LINC00342 and microRNA-203a-3p (miR-203a-3p) in colorectal cancer tissue and the prognosis of patients within 5 years after surgery. Methods Samples of colorectal cancer tissue and paracancer tissue of 133 patients with colorectal cancer were collected. Expression levels of LncRNA LINC00342 and miR-203a-3p were detected by fluorescence quantitative PCR. Survival and death were recorded after 5 years of follow-up. The LncRNA LINC00342 and miR-203a-3p expressions and clinicopathological parameters in patients under different conditions were compared. The correlation between expressions of LncRNA LINC00342 and miR-203a-3p in colorectal cancer tissue was analyzed, and their predictive value for the prognosis was also analyzed. Results The expression level of LncRNA LINC00342 was higher in colorectal cancer tissue than that in paracancer tissue, and the expression level of miR-203a-3p was lower in colorectal cancer tissue than that in paracancer tissue (P＜0.05). The expression levels of LncRNA LINC00342 and miR-203a-3p in colorectal cancer tissue were negatively correlated (P＜0.05). The proportion of patients with low tumor differentiation, TNM stage Ⅲ and lymph node metastasis were higher in the LncRNA LINC00342 high expression group and the miR-203a-3p low expression group than those in the LncRNA LINC00342 low expression group and the miR-203a-3p high expression group, respectively (P＜ 0.05). The 5-year overall survival rate after operation was lower in the LncRNA LINC00342 high expression group and the miR-203a-3p low expression group (P＜0.05). The proportion of patients with low tumor differentiation, TNM stage Ⅲ, lymph node metastasis, and higher expression level of LncRNA LINC00342 were higher in colorectal cancer tissue of the death group than those in the survival group, and the expression level of miR-203a-3p was lower than that in the survival group (P＜0.05). Low tumor differentiation, TNM stage Ⅲ, lymph node metastasis, high expression of LncRNA LINC00342 and low expression of miR-203a-3p were independent risk factors for death within 5 years after colorectal cancer surgery (P＜0.05). The combined predictive value of LncRNA LINC00342 and miR-203a-3p for prognosis was greater than that of individual prediction. Conclusion LncRNA LINC00342 is higher expressed and miR-203a-3p is lower expressed in colorectal cancer tissue, and the combined detection of the two is expected to become a clinical evaluation indicator for predicting postoperative survival. [ABSTRACT FROM AUTHOR]

Abstract Increased proinflammatory cytokines and infiltration of inflammatory cells in the stroma are important pathological features of type IIIA chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS-A), and the interaction between stromal cells and other cells in the inflammatory microenvironment is closely related to the inflammatory process of CP/CPPS-A. However, the interaction between stromal and epithelial cells remains unclear. In this study, inflammatory prostate epithelial cells (PECs) released miR-203a-3p-rich exosomes and facilitated prostate stromal cells (PSCs) inflammation by upregulating MCP-1 expression. Mechanistically, DUSP5 was identified as a novel target gene of miR-203a-3p and regulated PSCs inflammation through the ERK1/2/MCP-1 signaling pathway. Meanwhile, the effect of exosomes derived from prostatic fluids of CP/CPPS-A patients was consistent with that of exosomes derived from inflammatory PECs. Importantly, we demonstrated that miR-203a-3p antagomirs-loaded exosomes derived from PECs targeted the prostate and alleviated prostatitis by inhibiting the DUSP5-ERK1/2 pathway. Collectively, our findings provide new insights into underlying the interaction between PECs and PSCs in CP/CPPS-A, providing a promising therapeutic strategy for CP/CPPS-A.

Increased proinflammatory cytokines and infiltration of inflammatory cells in the stroma are important pathological features of type IIIA chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS-A), and the interaction between stromal cells and other cells in the inflammatory microenvironment is closely related to the inflammatory process of CP/CPPS-A. However, the interaction between stromal and epithelial cells remains unclear. In this study, inflammatory prostate epithelial cells (PECs) released miR-203a-3p-rich exosomes and facilitated prostate stromal cells (PSCs) inflammation by upregulating MCP-1 expression. Mechanistically, DUSP5 was identified as a novel target gene of miR-203a-3p and regulated PSCs inflammation through the ERK1/2/MCP-1 signaling pathway. Meanwhile, the effect of exosomes derived from prostatic fluids of CP/CPPS-A patients was consistent with that of exosomes derived from inflammatory PECs. Importantly, we demonstrated that miR-203a-3p antagomirs-loaded exosomes derived from PECs targeted the prostate and alleviated prostatitis by inhibiting the DUSP5-ERK1/2 pathway. Collectively, our findings provide new insights into underlying the interaction between PECs and PSCs in CP/CPPS-A, providing a promising therapeutic strategy for CP/CPPS-A. [ABSTRACT FROM AUTHOR]

Objective To explore the effects of miR-203a-3p on the invasion and migration of esophageal cancer cells and to analyze the targeted regulatory relationship with Survivin. Methods Esophageal cancer TE-1 cells and normal esophageal mucosal epithelial HEEC cells in logarithmic growth phase were collected. The miR-203a-3p and Survivin mRNA were tested by RT-qPCR. The targeted regulatory relationship between miR-203a-3p and Survivin was analyzed by dual luciferase reporter assay. The TE-1 cells were divided into the control group, miR-203a-3p simulation group, miR203a-3p inhibitory group, and negative control group, respectively. Cells in the miR-203a-3p simulation group were transfected with miR-203a-3p mimic, miR-203a-3p-inhibited group with miR-203a-3p inhibitor, and negative control group with miR-203a-3p NC, while cells in the control group were not transfected. Transfection efficiency was verified by RT-qPCR. Cell viability was measured by MTT at 2, 12, 24, 36 and 48 h after transfection, cell migration was measured by Scratch assay and cell invasion was measured by Transwell invasion assay. Results The mRNA expression of miR-203a3p was lower and the mRNA expression of Survivin was higher in the esophageal cancer cells than in the normal esophageal mucosal epithelial cells(both P<0. 05). TargetScan database analysis showed that the Survivin gene had seven consecutive nucleotide sequences at the 3′UTR end that could be complementary to miR-203a-3p. The result of dual luciferase reporter assay showed that TE-1 cells co-transfected with Survivin-WT and plasmid-miR-203a-3p mimic plasmids had lower activity than other cells(P<0. 05). The cell viability at 12, 24, 36 and 48 h was as follows: the miR-203a-3p inhibition group > the control group and the negative control group > the miR-203a-3p simulation group(all P<0. 05). The cell migration distance and the number of invasive cells were in the following order: the miR-203a-3p inhibition group > the control group and negative control group> the miR-203a-3p simulation group(all P<0. 05). Conclusion High expression of miR-203a-3p inhibits the migration and invasion of esophageal cancer cells, and the mechanism may be related to the targeted negative regulation of Survivin. [ABSTRACT FROM AUTHOR]

Abstract Background Long noncoding RNAs (lncRNAs) have been identified as important regulatory factors implicated in a wide array of diseases, including various forms of cancer. However, the roles of most lncRNAs in the progression of gastric cancer (GC) remain largely unexplored. This study investigates the biological function and underlying mechanism of a novel lncRNA, XLOC_004787 in GC. Methods The location of XLOC_004787 in GES-1 cells and HGC-27 cells were detected by fluorescence in situ hybridization (FISH) assay. The expression levels of XLOC_004787 were assessed using quantitative real-time fluorescence PCR (qRT-PCR) in various cell lines, including GES-1, MGC-803, MKN-45, BGC-823, SGC-7901, and HGC-27 cells. Functional assays such as Transwell migration, cell counting kit-8 (CCK-8), and colony formation experiments were employed to analyze the effects of XLOC_004787 and miR-203a-3p on cell migration and proliferation. Protein levels associated with GC in these cell lines were examined by Western blotting. The intracellular localization of β-catenin and P-Smad2/3 was assessed using immunofluorescence (IF) assay. Additionally, the interaction between XLOC_004787 and miR-203a-3p was investigated using a dual luciferase assay. Results XLOC_004787 was localized at both the cytoplasm and nucleus of GES-1 cells and HGC-27 cells. Compared to normal tissues and GES-1 cells, XLOC_004787 expression was significantly upregulated in GC tissues and cells, with the highest and lowest expression observed in SGC-7901 and HGC-27 cells, respectively. Furthermore, a reduced expression of XLOC_004787 was seen to inhibit migration and proliferation in SGC-7901 cells. Western blotting analysis revealed that a decrease in XLOC_004787 expression correspondingly decreased the expression of N-cadherin, mmp2, mmp9, Snail, Vimentin, β-catenin, C-myc, Cyclin D1, and TGF-β, while concurrently increasing E-cadherin expression. This was also associated with diminished expression of P-Smad2/3 in relation to Smad2/3, and reduced P-Gsk3β expression in comparison to Gsk3β. Additionally, the nuclear entry of P-Smad2/3 and β-catenin was reduced by lower XLOC_004787 expression. Amplifying XLOC_004787 expression via pcDNA_XLOC_004787 suggested a potential for cancer promotion. Notably, XLOC_004787 was found to negatively regulate mir-203a-3p expression, with potential binding sites identified between the two. Higher mir-203a-3p expression was observed to decrease migration and proliferation, and enhance E-cadherin expression. Conversely, suppression of mir-203a-3p expression suggested a potential promotion of proliferation and migration in GC cells. Conclusions These results suggest that XLOC_004787, found to be upregulated in GC tissues, potentially promotes proliferation and migration in GC cells. This occurs through the activation of TGF-β and Wnt/β-catenin signaling pathways and the expression of EMT-related proteins. Additionally, XLOC_004787 may influence cell migration and proliferation by modulating the signaling pathway via the adsorption and inhibition of mir-203a-3p.

Background: Long noncoding RNAs (lncRNAs) have been identified as important regulatory factors implicated in a wide array of diseases, including various forms of cancer. However, the roles of most lncRNAs in the progression of gastric cancer (GC) remain largely unexplored. This study investigates the biological function and underlying mechanism of a novel lncRNA, XLOC_004787 in GC. Methods: The location of XLOC_004787 in GES-1 cells and HGC-27 cells were detected by fluorescence in situ hybridization (FISH) assay. The expression levels of XLOC_004787 were assessed using quantitative real-time fluorescence PCR (qRT-PCR) in various cell lines, including GES-1, MGC-803, MKN-45, BGC-823, SGC-7901, and HGC-27 cells. Functional assays such as Transwell migration, cell counting kit-8 (CCK-8), and colony formation experiments were employed to analyze the effects of XLOC_004787 and miR-203a-3p on cell migration and proliferation. Protein levels associated with GC in these cell lines were examined by Western blotting. The intracellular localization of β-catenin and P-Smad2/3 was assessed using immunofluorescence (IF) assay. Additionally, the interaction between XLOC_004787 and miR-203a-3p was investigated using a dual luciferase assay. Results: XLOC_004787 was localized at both the cytoplasm and nucleus of GES-1 cells and HGC-27 cells. Compared to normal tissues and GES-1 cells, XLOC_004787 expression was significantly upregulated in GC tissues and cells, with the highest and lowest expression observed in SGC-7901 and HGC-27 cells, respectively. Furthermore, a reduced expression of XLOC_004787 was seen to inhibit migration and proliferation in SGC-7901 cells. Western blotting analysis revealed that a decrease in XLOC_004787 expression correspondingly decreased the expression of N-cadherin, mmp2, mmp9, Snail, Vimentin, β-catenin, C-myc, Cyclin D1, and TGF-β, while concurrently increasing E-cadherin expression. This was also associated with diminished expression of P-Smad2/3 in relation to Smad2/3, and reduced P-Gsk3β expression in comparison to Gsk3β. Additionally, the nuclear entry of P-Smad2/3 and β-catenin was reduced by lower XLOC_004787 expression. Amplifying XLOC_004787 expression via pcDNA_XLOC_004787 suggested a potential for cancer promotion. Notably, XLOC_004787 was found to negatively regulate mir-203a-3p expression, with potential binding sites identified between the two. Higher mir-203a-3p expression was observed to decrease migration and proliferation, and enhance E-cadherin expression. Conversely, suppression of mir-203a-3p expression suggested a potential promotion of proliferation and migration in GC cells. Conclusions: These results suggest that XLOC_004787, found to be upregulated in GC tissues, potentially promotes proliferation and migration in GC cells. This occurs through the activation of TGF-β and Wnt/β-catenin signaling pathways and the expression of EMT-related proteins. Additionally, XLOC_004787 may influence cell migration and proliferation by modulating the signaling pathway via the adsorption and inhibition of mir-203a-3p. [ABSTRACT FROM AUTHOR]

Objective To explore the molecular mechanism of regulation on the proliferation and apoptosis in hepatocellular carcinoma(HCC) cells by miR-203a-3p. Methods RT-qPCR was used to detect the expression of miR-203 a-3p in the sample of liver cancer tissues and liver cancer cell lines. The HepG2 cell model expressing miR-203a-3p was established. Cell proliferation was observed by MTT method and the apoptosis of cells was detected by flow cytometry. Plate colony formation assay was used to detect clone formation and cell scratch assay was used to detect cell migration. Expression profile chip was applied in the detection of mRNA and ELISA was used to detect the secretion of transforming growth factor-β1 (TGF-β1). TGF-β1 protein expression was examined by Western blod technology. Results miR-203a-3p was weekly expressed in HCC tissues (PPPPPPPPPPPConclusions miR-203a-3p inhibits proliferation of human hepatocellular carcinoma cell lines, promotes apoptosis and inhibits the expression of TGF-β1 protein.

Circular RNA has been reported to participate in human diseases including diabetic nephropathy (DN). However, the role and mechanism of circ_0123996 in DN need to be further explored. Relative expression levels of circ_0123996, microRNA (miR)‐203a‐3p, SRY‐box 6 (SOX6), and inflammatory cytokines were determined using quantitative real‐time PCR. Western blot analysis was used to detect the protein expression of SOX6 and fibrosis‐related markers. Cell proliferation was measured using the Cell Counting Kit 8 assay. The interaction between miR‐203a‐3p and circ_0123996 or SOX6 was verified using the dual‐luciferase reporter assay. The circ_0123996 and SOX6 expression were increased and the miR‐203a‐3p expression was decreased in high glucose‐induced mesangial cells. Silenced circ_0123996 could hinder the proliferation, inflammation, and fibrosis of mesangial cells. In terms of mechanism, circ_0123996 could sponge miR‐203a‐3p to positively regulate SOX6 expression. Function experiments revealed that miR‐203a‐3p inhibitor could abolish the regulation of circ_0123996 silencing on mesangial cell proliferation, inflammation, and fibrosis. In addition, the knockdown of SOX6 could inhibit mesangial cell proliferation, inflammation, and fibrosis. Also, SOX6 overexpression could reverse the regulation of circ_0123996 silencing on mesangial cell progression. In summary, our data revealed that circ_0123996 promoted the proliferation, inflammation, and fibrosis of mesangial cells via modulating the miR‐203a‐3p/SOX6 axis, suggesting that circ_0123996 might be a target for alleviating DN progression. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of miR ‑203a ‑3p on the biological behavior of hepatocellular carcinoma (HCC) cells and its related molecular mechanism. Methods The miR‑203a‑3p mimics (miR‑203a‑3p mimics), negative control (miR‑NC mimics), LIM and SH3 protein 1 (LASP1) overexpression plasmid (pcDNS‑LASP1) and negative control plasmid (pcDNA‑NC) were transfected into HepG2 cells. The expressions of miR‑203a‑3p and LASP1 mRNA were detected by qRT‑PCR; cell proliferation was detected by the CCK‑8 method and the allogeneic transplantation experiment; cell migration ability was detected by Wound healing assay; cell invasion ability was detected by Transwell; cell apoptosis was detected by Annexin V‑FITC / PI method; Double luciferase reporter was used to detect the targeting relationship between miR‑203a‑3p and LASP1; Western blot was used to detect the protein expressions of LASP1, protein kinase B (Akt), phosphorylated Akt (p‑Akt), glycogen synthase kinase‑3β (GSK‑3β), phosphorylated GSK‑3β (p‑GSK‑3β) and Snail. Results Compared with those in the miR‑NC group, the proliferation activity, migration rate, invasion number, LASP1 mRNA and protein expressions, the ratio of p‑Akt/Akt and p‑GSK‑3β/GSK‑3β, and the protein expression of Snail of HepG2 cells in the miR‑203a‑3p group were significantly decreased; the volume and mass of transplanted tumor in mice were significantly decreased; the apoptosis rate was significantly increased (all P<0.01). Targetscan software prediction showed that miR ‑ 203a ‑ 3p had a targeting relationship with LASP1. Compared with that of LASP1‑Wt+miR‑NC group, the relative luciferase activity of LASP1‑Wt+miR‑203a‑3p group was signifi‑ cantly decreased (P<0.001). Compared with those of the miR‑203a‑3p+pcDNA‑NC group, the proliferation activity, migration rate, invasion number, p‑Akt/Akt and p‑GSK‑3 β/GSK‑3 β ratio, the protein expression of Snail protein of HepG2 cells in the miR‑203a‑3p+ LASP1 group were significantly increased; the volume and mass of transplanted tumor in mice were also significantly increased; the apoptosis rate was significantly decreased (all P<0.01). Conclusions The miR‑203a‑3p may regulate the activity of Akt/GSK‑3β/Snail signaling pathway by targeting the inhibition of LASP1 expression, thereby regulating the biological behavior of HCC cells. [ABSTRACT FROM AUTHOR]

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Many genes and miRNAs have been shown to be associated with the pathogenesis of endometriosis. TP63 (p63) is implicated in lineage specification, proliferative potential, differentiation, cell death and survival. The ABL1 proto-oncogene encodes a cytoplasmic and nuclear protein tyrosine kinase implicated in cell differentiation, cell division, and cell adhesion. Moreover, hsa-miR-203a-3p was reported to play pivotal roles in tumor progression by targeting multiple genes, including ABL1 and TP63. The aim of this study was to investigate the expression of ABL1, TP63, and miR-203a-3p in endometriosis. This study included 30 women with endometriosis (stage III: n = 12 and stage IV: n = 18) and 30 age-matched controls. Total RNA extraction and cDNA synthesis were performed, and a quantitative polymerase chain reaction technique was used to determine the expression of miR-203a-3p, TP63, and ABL1. TP63 and ABL1 were significantly overexpressed in stages III and IV endometriosis as compared to controls (p <.0001). Moreover, overexpression of ABL1 and TP63 was observed in stage IV compared to stage III (p =.0006 and p =.0002, respectively). Furthermore, significant increase miR-203a-3p expression has been seen in stage IV endometriosis compared to controls (p =.006). The expression of miR-203a-3p in stage III was not significant compared to stage IV and control (p =.33 and p =.43, respectively). It is concluded that miR-203a-3p, ABL1 and TP63 gene expression is altered in the endometrium of patients with endometriosis. It is also suggested that miR-203a-3p, ABL1, and TP63 might be candidate factors for the pathogenesis of endometriosis and suggesting its therapeutic potential in endometriosis. [ABSTRACT FROM AUTHOR]

In resected non-small cell lung cancer (NSCLC), post-surgical recurrence occurs in around 40% of patients, highlighting the necessity to identify relapse biomarkers. An analysis of the extracellular vesicle (EV) cargo from a pulmonary tumor-draining vein (TDV) can grant biomarker identification. We studied the pulmonary TDV EV-miRNAome to identify relapse biomarkers in a two-phase study (screening and validation). In the screening phase, a 17-miRNA relapse signature was identified in 18 selected patients by small RNAseq. The most expressed miRNA from the signature (EV-miR-203a-3p) was chosen for further validation. Pulmonary TDV EV-miR-203a-3p was studied by qRT-PCR in a validation cohort of 70 patients, where it was found to be upregulated in relapsed patients (p = 0.0194) and in patients with cancer spread to nearby lymph nodes (N+ patients) (p = 0.0396). The ROC curve analysis showed that TDV EV-miR-203a-3p was able to predict relapses with a sensitivity of 88% (AUC: 0.67; p = 0.022). Moreover, patients with high TDV EV-miR-203a-3p had a shorter time to relapse than patients with low levels (43.6 vs. 97.6 months; p = 0.00703). The multivariate analysis showed that EV-miR-203a-3p was an independent, predictive and prognostic post-surgical relapse biomarker. In conclusion, pulmonary TDV EV-miR-203a-3p is a promising new relapse biomarker for resected NSCLC patients. [ABSTRACT FROM AUTHOR]

Background: Biomarkers, such as microRNAs, are helpful in diagnosing colorectal cancer, regulating disease progression, predicting disease recurrence, and determining therapy success. This research aimed to look at the clinicopathological characteristics of serum miRNA-203a-3p expression in colorectal cancer patients. Methods and results: This case–control study was conducted on 43 patients with colorectal cancer and 43 healthy individuals. After RNA extraction, cDNA was synthesized. The expression of miR-203a-3p was measured using RT-qPCR. Demographic and histochemical data were extracted from patient documents. SPSS and GraphPad Prism software were used to analyze the data. The expression of miR-203a-3p in CRC patients was 2.39 times lower than in the control group (p < 0.0001). The miR-203a-3p expression was significantly lower in the CRC tumor stages, tumor grades, and lymph node metastasis compared to the control group (p < 0.0001 each). The ROC curves showed that the AUC was 0.73, and the best cut-point based on the Youden index was 0.3954, 0.7105, 0.5087, and 0.4868 for detecting colorectal cancer (p = 0.0002), tumor grade (p = 0.006), tumor stage (p = 0.001), and lymph node metastasis (p = 0.0011) compared to the control group, respectively. The binary logistic regression analysis was performed on the correlation between BMI, smoking, and cancer inheritance with miR-203a-3p in cancer and control groups. Conclusion: This study's findings revealed that serum miR-203a-3p is a fair non-invasive molecular biomarker for diagnosing and progressing tumor grade, tumor stage, and lymph node metastasis in colorectal cancer. However, further research with higher statistical numbers is needed to strengthen the correlation and be used for diagnostic applications. [ABSTRACT FROM AUTHOR]

Abstract Background Liver metastasis is the most common cause of death in patients with colorectal cancer (CRC). Phosphatase of regenerating liver-3 induces CRC metastasis by epithelial-to-mesenchymal transition, which promotes CRC cell liver metastasis. Mesenchymal-to-epithelial transition (MET), the opposite of epithelial-to-mesenchymal transition, has been proposed as a mechanism for the establishment of metastatic neoplasms. However, the molecular mechanism of MET remains unclear. Methods Using Immunohistochemistry, western blotting, invasion assays, real-time quantitative PCR, chromatin immunoprecipitation, luciferase reporter assays, human miRNA arrays, and xenograft mouse model, we determined the role of hepatocyte exosome-derived miR-203a-3p in CRC MET. Results In our study, we found that miR-203a-3p derived from hepatocyte exosomes increased colorectal cancer cells E-cadherin expression, inhibited Src expression, and reduced activity. In this way miR-203a-3p induced the decreased invasion rate of CRC cells. Coclusion MiR-203a-3p derived from hepatocyte exosomes plays an important role of CRC cells to colonize in liver.

Bone marrow mesenchymal stem cells (BMSCs) differentiate into chondrocytes under appropriate conditions, providing a method for the treatment of bone- and joint-related diseases. Previously, we found that mulberry (Morus nigra) promoted the chondrogenic differentiation of BMSCs. Although the mechanism of action and active ingredients remain unknown, several studies describe the involvement of micro-RNAs. We obtained BMSCs from the bone marrow of Sprague Dawley rats. Cell Counting Kit-8 assays showed that maclurin (25 μg/mL) treatment was not toxic to BMSCs, and compared with untreated controls, maclurin upregulated Sox9 and Col2a expression. Quantitative-PCR revealed that miR-203a-3p levels decreased significantly during chondrogenic differentiation of BMSCs promoted by maclurin. Compared with treatment with an miR-203a-3p inhibitor, miR-203a-3p mimic inhibited expression of Sox9 and Col2a as evidenced by immunofluorescence staining and Western blotting. Smad1 was identified as a key target gene of miR-203a-3p according to biological-prediction software, and miR-203a-3p negatively regulated its transcription and translation in the dual-luciferase reporter gene assay and Western blotting. Sox9 and Col2a expression was downregulated following transfection of short interfering Smad1 (siSmad1) plasmids into BMSCs. We elucidated how maclurin promotes the chondrogenic differentiation of BMSCs by regulating miR-203a-3p/Smad1, which provides a strategy for future exploration of osteoarthritis therapy through cell transplantation. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) has a high incidence in SoutheastAsia and China. This study aims to investigate the effect of miR-203a-3p and vascular endothelial growth factor-C (VEGF-C) on nasopharyngeal carcinoma. In this study, we investigate the transfection of miR-203a-3p mimics and the ability of miR-203a-3p to inhibit in nasopharyngeal carcinoma cell line 5-8F and C666-1, the expression levels of protein AKT, p-AKT in VEGF-C and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signal pathway by plate clone formation experiment, flow cytometer PI staining method, transwell cell experiment, vasculogenic mimicry experiment, and Western blot. The results showed that miR-203a-3p in the nasopharyngeal carcinoma cell line significantly decreased, while VEGF-C in nasopharyngeal carcinoma tissues and cell lines significantly increased. Furthermore, miR-203a-3p inhibited the proliferation of nasopharyngeal carcinoma cells and blocked the cell cycle of nasopharyngeal carcinoma in the G0 /G1 phase, reduced the vasculogenic phenomena and epithelialmesenchymal transition of nasopharyngeal carcinoma cells, and effectively inhibited the growth of nasopharyngeal carcinoma in vivo. The low expression of VEGF-C can inhibit the proliferation, vasculogenic mimicry, and epithelialmesenchymal transition of nasopharyngeal carcinoma cells. We found that miR-203a-3p was expressed to a low degree in nasopharyngeal carcinoma. Furthermore, miR-203a-3p regulated the PI3K/AKT signal pathway by downregulating the expression of VEGF-C, thereby inhibiting the proliferation, migration, invasion, vasculogenic mimicry, epithelialmesenchymal transition, and other malignant biological characteristics of nasopharyngeal carcinoma cells. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of miR-203a-3p on the proliferation, migration and invasion ability of pancreatic cancer BxPC-3 cells. Methods: The Cancer Genome Atlas (TCGA) database was used to screen the differentially expressed miRNAs between pancreatic cancer tissues and paracancerous tissues, and to analyze the survival rate and clinical stage of pancreatic cancer patients with high or low miRNAexpression; TarBase was used for the cancer related GO function and KEGG pathway analysis of the miRNAs,DIANATools, miRDB and TargetScan websites were used to predict the target genes of miR-203a-3p. miR-203a-3p mimic and NC mimic, miR-203a-3p inhibitor and NC inhibitor were transfected into BxPC-3 cells. The expression levels of miR-203a-3p, miR-192-5p and miR-451a in normal pancreatic epithelial HPNE cells and pancreatic cancer cells were detected by qPCR. The proliferation, migration, invasion and colony formation abilities of BxPC-3 cells were detected by CCK-8, Transwell chamber assay and Colony formation assay, respectively. Results: A total of 18 differentially expressed miRNAs in pancreatic cancer tissues were screened out by TCGA database, among which miR-203a- 3p, miR-192-5p and miR-451a were species-conservative and significantly correlated with clinical cancer stage, cell cycle and survival rate of pancreatic cancer patients (all P<0.05); Bioinformatics tool predicted that PPM1A might be the candidate target gene of miR- 203a-3p and could interact with multiple genes. miR-203a-3p, miR-192-5p and miR-451a were highly expressed in BxPC-3 and Aspc- 1 cells (all P<0.001). In miR-203a-3p mimic group, the expression level of miR-203a-3p and the proliferation, migration and invasion ability of BxPC-3 cells were significantly increased (all P<0.01); however, in miR-203a-3p inhibitor group, the expression level of miR-203a-3p and the ability of cell proliferation, migration and invasion were significantly decreased (all P<0.01). Conclusion: miR-203a-3p is highly expressed in pancreatic cancer tissues and cells, and its expression is related to the survival and clinical stage of patients. miR-203a-3p may regulate the proliferation, migration and invasion of BxPC-3 cells. [ABSTRACT FROM AUTHOR]

Abstract Objective To investigate whether miR-203a-3p can regulate the biological behaviors of ovarian cancer cells by targeting ATM to affect the Akt/GSK-3β/Snail signaling pathway. Methods The expression levels of miR-203a-3p and ATM were detected by qRT-PCR, immunohistochemical staining and Western blotting in ovarian cancer tissues and adjacent normal tissues obtained from 152 subjects. A dual-luciferase reporter gene assay was performed to verify the relationship between miR-203a-3p and ATM. Human ovarian cancer cell lines (A2780 and SKOV3) were used to generate the Blank, miR-NC, miR-203a-3p mimic, Control siRNA, ATM siRNA, and miR-203a-3p inhibitor + ATM siRNA groups. The biological behaviors of ovarian cancer cells were evaluated by CCK-8, wound healing, and Transwell invasion assays, annexin V-FITC/PI staining and flow cytometry. The levels of Akt/GSK-3β/Snail pathway-related proteins were assessed by Western blotting. Results Ovarian cancer tissues showed lower miR-203a-3p levels and higher ATM levels than adjacent normal tissues, both of which were associated with the FIGO stage, grade and prognosis of ovarian cancer. As confirmed by a dual-luciferase reporter gene assay, miR-203a-3p could target ATM. Furthermore, the miR-203a-3p mimic had multiple effects, including the inhibition of the proliferation, invasion and migration of A2780 and SKOV3 cells, the promotion of cell apoptosis, the arrest of the cell cycle at the G1 phase, and the blockage of the Akt/GSK-3β/Snail signaling pathway. ATM siRNA had similar effects on the biological behaviors of ovarian cancer cells, and these effects could be reversed by a miR-203a-3p inhibitor. Conclusion miR-203a-3p was capable of hindering proliferation, migration, and invasion and facilitating the apoptosis of ovarian cancer cells through its modulation of the Akt/GSK-3β/Snail signaling pathway by targeting ATM, and therefore it could serve as a potential therapeutic option for ovarian cancer.

Abstract Background As a subclass of noncoding RNAs, circular RNAs (circRNAs) have been demonstrated to play a critical role in regulating gene expression in eukaryotes. Recent studies have revealed the pivotal functions of circRNAs in cancer progression. However, little is known about the role of circTADA2A, also named hsa_circ_0043278, in osteosarcoma (OS). Methods CircTADA2A was selected from a previously reported circRNA microarray comparing OS cell lines and normal bone cells. QRT-PCR was used to detect the expression of circTADA2A in OS tissue and cell lines. Luciferase reporter, RNA immunoprecipitation (RIP), RNA pull-down and fluorescence in situ hybridization (FISH) assays were performed to confirm the binding of circTADA2A with miR-203a-3p. OS cells were stably transfected with lentiviruses, and Transwell migration, Matrigel invasion, colony formation, proliferation, apoptosis, Western blotting, and in vivo tumorigenesis and metastasis assays were employed to evaluate the roles of circTADA2A, miR-203a-3p and CREB3. Results Our findings demonstrated that circTADA2A was highly expressed in both OS tissue and cell lines, and circTADA2A inhibition attenuated the migration, invasion and proliferation of OS cells in vitro as well as tumorigenesis and metastasis in vivo. A mechanistic study revealed that circTADA2A could readily sponge miR-203a-3p to upregulate the expression of CREB3, which was identified as a driver gene in OS. Furthermore, miR-203a-3p inhibition or CREB3 overexpression could reverse the circTADA2A silencing-induced impairment of malignant tumor behavior. Conclusions CircTADA2A functions as a tumor promoter in OS to increase malignant tumor behavior through the miR-203a-3p/CREB3 axis, which could be a novel target for OS therapy.

Abstract Background Earlier diagnosis is beneficial for the prognosis of hepatocellular carcinoma (HCC). Alpha fetoprotein (AFP) is the most widely used biomarker for HCC, but its sensitivity and specificity are only 60 and 90%, respectively. Therefore, it is of great clinical significance to identify early prognostic biomarkers for HCC, especially a blood-based biomarker as it offers several advantages over tissue-based biomarkers. Trefoil factor 3 (TFF3), a novel secretory protein, was over-expressed in HCC tissues, indicating it might be a blood-based biomarker for HCC. In addition, circulating microRNAs have been investigated as biomarkers for HCC, indicating that miR-7-5p and miR-203a-3p, which are reported or predicted to target TFF3, also hold promise as blood-based biomarkers for HCC. Methods We enrolled 43 patients who were firstly diagnosed HCC and matched 47 control subjects without HCC. The levels of TFF3, miR-7-5p and miR-203a-3p were tested in the plasma of HCC patients. Moreover, we assayed the correlation of TFF3 with its related micro RNAs, miR-7-5p and miR-203a-3p, and evaluated their predictive powers for HCC. Results Decrease of TFF3 was associated with increase of miR-203a-3p in the plasma of HCC patients and they displayed potent predictive powers for HCC diagnosis. However, there was no significant change of plasma miR-7-5p between HCC and control group. Conclusion Decrease of TFF3 correlated with increase of miR-203a-3p in the plasma of HCC patients and they could be additional biomarkers to improve sensitivity and specificity in the diagnosis of HCC.

Bronchopulmonary dysplasia (BPD) is characterized by impaired vascular and alveolar development, and the underlying molecular mechanisms have remained elusive. MicroRNAs are important players in various biological functions including the pathogenesis of BPD. The present study aimed to examine the expression of miR-203a-3p in the peripheral blood of BPD patients and elucidate the mechanisms underlying miR-203a-3p-mediated progression of BPD. We examined the expression of miR-203a-3p in the peripheral blood of BPD patients and found that miR-203a-3p was up-regulated in the patients. Additionally, the mRNA expression levels of vascular endothelial growth factor A (VEGFA) and hypoxia-inducible factor-1alpha were down-regulated in the BPD patients. Further in vitro studies showed that miR-203a-3p suppressed the expression of VEGFA in RLE-6TN cells by targeting the VEGFA 3′ untranslated region. Overexpression of miR-203a-3p inhibited the viability of RLE-6TN cells and induced cell apoptosis, whereas the knockdown of miR-203a-3p exerted opposite effects. VEGFA treatment significantly attenuated the increase in the RLE-6TN cell apoptotic rates induced by miR-203a-3p overexpression; while VEGFA knockdown significantly increased the cell apoptotic rates of RLE-6TN cells, which was partially reversed by the treatment with miR-203a-3p inhibitor. Furthermore, miR-203a-3p was up-regulated, whereas VEGFA was down-regulated in the lung tissues of BPD rats, and sequestration of the expression of miR-203a-3p prevented hyperoxia-induced lung damage, increased VEGFA mRNA and protein expression levels, and promoted the protein expression of ERK, PI3K, and p38 in the lung tissues of BDP rats. In summary, the findings of our study indicate that miR-203a-3p knockdown alleviates hyperoxia-induced lung tissue damage in the BPD rat model, and its effect may be associated with the up-regulation of VEGF. [ABSTRACT FROM AUTHOR]

Background: Hypertrophic scar (HS) is a common fibroproliferative skin disease that currently has no truly effective therapy. Given the importance of phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) in hypertrophic scar formation, the development of therapeutic strategies for endogenous inhibitors against PIK3CA is of great interest. Here, we explored the molecular mechanisms underlying the protective effects of miR-203a-3p (PIK3CA inhibitor) against excessive scar., Methods: Bioinformatic analysis, immunohistochemistry, immunofluorescence, miRNA screening and fluorescence in situ hybridization assays were used to identify the possible pathways and target molecules mediating HS formation. A series of in vitro and in vivo experiments were used to clarify the role of PIK3CA and miR-203a-3p in HS. Mechanistically, transcriptomic sequencing, immunoblotting, dual-luciferase assay and rescue experiments were executed., Results: Herein, we found that PIK3CA and the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway were upregulated in scar tissues and positively correlated with fibrosis. We then identified miR-203a-3p as the most suitable endogenous inhibitor of PIK3CA. miR-203a-3p suppressed the proliferation, migration, collagen synthesis and contractility as well as the transdifferentiation of fibroblasts into myofibroblasts in vitro , and improved the morphology and histology of scars in vivo . Mechanistically, miR-203a-3p attenuated fibrosis by inactivating the PI3K/AKT/mTOR pathway by directly targeting PIK3CA., Conclusions: PIK3CA and the PI3K/AKT/mTOR pathway are actively involved in scar fibrosis and miR-203a-3p might serve as a potential strategy for hypertrophic scar therapy through targeting PIK3CA and inactivating the PI3K/AKT/mTOR pathway., Competing Interests: The authors declare that they have no competing interests., (© The Author(s) 2024. Published by Oxford University Press.)

BACKGROUND: EGFR-mutant lung cancer inevitably develops resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). OBJECTIVE: To investigate the clinical relevance of microRNAs (miRNAs) in TKI therapy response and resistance. METHODS: We performed a miRNA PCR array analysis and used The Cancer Genome Atlas (TCGA) database to identify potential miRNAs related to EGFR TKIs resistance. We then correlated miRNA expression in 70 surgical and 50 malignant pleural effusion specimens with patient outcomes in those with non-small cell lung carcinoma. Molecular manipulation was performed in EGFR mutant lung cancer cells to assess the effect of miR-200c-3p on cell migratory ability and EGFR-TKI sensitivity. RESULTS: We identified miR-200c-3p and miR-203a-3p as potential EGFR TKI resistance regulators via their modulation of epithelial-to-mesenchymal transition (EMT). MiR-200c-3p and miR-203a-3p were down-regulated in EGFR TKI-resistant cell lines. Progression-free survival (PFS) with EGFR-TKI treatment of patients with high miR-200c-3p expression, but not miR-203a-3p, in the specimens was significantly longer than that of patients with low expression. MiR-200c-3p overexpression inhibited the EMT process in EGFR TKI resistance cell lines and promoted cell death. MiR-200c-3p silencing in EGFR TKI sensitive cell lines increased drug resistance. CONCLUSION: MiR-200c-3p plays a role in sensitivity to EGFR TKIs via modulating EMT process. [ABSTRACT FROM AUTHOR]

Aim: We aimed to investigate the clinical significance and biological function of miR-203a-3p in non-small-cell lung cancer (NSCLC). Methods: The association between miR-203a-3p expression and clinicopathological parameters in NSCLC was assessed by χ2 test. Kaplan–Meier method and Cox regression model were applied to evaluate the prognosis value of miR-203a-3p. The biological function of miR-203-3p was explored using CCK-8 and transwell assays. Results: Significantly downregulated miR-203a-3p was associated with TNM stage, lymph node metastasis and poor prognosis. AVL9 was identified as a direct target of miR-203a-3p. Functionally, we found overexpression of miR-203a-3p inhibited cell proliferation, migration and invasion in NSCLC cells by targeting AVL9. Conclusion: Collectively, targeting the miR-203a-3p/AVL9 axis might help to develop useful therapeutic target for NSCLC. [ABSTRACT FROM AUTHOR]

This study was designed to investigate the role of miR-203a-3p in hepatocyte proliferation. Data analysis showed that up-regulation of miR-203a-3p increased the cell viability and cell proliferation, and inhibited apoptosis. Further experiments demonstrated that PTEN was a target gene of miR-203a-3p, and miR-203a-3p targeted PTEN to regulate the above functions. Overexpression of PTEN partially reversed the inhibition of PTEN and the activation of p-Akt/Akt induced by miR-203a-3p mimic. Our study revealed that miR-203a-3p might activate PI3K/Akt signaling pathway by inhibiting PTEN expression, thereby promoting cell proliferation. Up-regulation of miR-203a-3p promoted growth and inhibited apoptosis of rat BRL-3A hepatocyte. [ABSTRACT FROM AUTHOR]

The pivotal roles of long noncoding RNAs have been reported in various cancers. Recently, FBXL19‐AS1 was proposed to be involved in tumor progression. However, its role in lung adenocarcinoma (LUAD) remains elusive. In this study, we observed that FBXL19‐AS1 was significantly upregulated in LUAD tissues and high FBXL19‐AS1 expression in LUAD was associated with a poor prognosis. Nevertheless, miR‐203‐3p showed the opposite effect. Moreover, cell viability and apoptosis analysis revealed that FBXL19‐AS1 knockdown could arrest LUAD cells in G0/G1 phase and inhibit cell proliferation, migration and invasion in vitro and inhibited LUAD tumor progress in vivo. Mechanistically, we identified FBXL19‐AS1 could act as a miR‐203a‐3p sponge using dual‐luciferase reporter assay. In addition, we demonstrated that downregulation of miR‐203a‐3p reversed growth inhibition of LUAD cells caused by FBXL19‐AS1 knockdown. Finally, FBXL19‐AS1/miR‐203a‐3p axis was found to associate with baculoviral IAP repeat‐containing protein 5.1‐A‐like (survivin), distal‐less homeobox 5, E2F transcription factor 1, and zinc finger E‐box binding homeobox 2 to regulate metastasis in LUAD cells. This study reveals a significance and mechanism of FBXL19‐AS1 in LUAD proliferation and metastasis and offers a potential prognostic marker and a therapeutic target for patients with LUAD. [ABSTRACT FROM AUTHOR]

Proliferative diabetic retinopathy (PDR) is a common complication of diabetes mellitus, characterized by abnormal retinal angiogenesis. MicroRNA‐203‐3p (miR‐203‐3p) was found to be down‐regulated in a murine model of proliferative retinopathy. This study was performed to explore the role of miR‐203a‐3p in retinal angiogenesis of PDR. Firstly, a rat OIR model, which was used to mimic PDR, was established and the OIR rats were treated with scrambled control or miR‐203a‐3p agomir by intravitreal injection. The results showed that the level of miR‐203a‐3p was decreased in OIR rats, and forced over‐expression of miR‐203a‐3p inhibited OIR‐induced retinal angiogenesis as evidenced by reduced blood vessel profiles and CD31 expression. OIR‐induced up‐regulation of VEGFA, HIF‐α, PCNA, and MMPs in the retina was also counteracted by miR‐203a‐3p. Additionally, high glucose (HG)‐induced proliferation, migration and tube formation of human retinal microvascular endothelial cells (HRMECs) were also dampened by the up‐regulation of miR‐203a‐3p. Dual‐luciferase reporter assay showed that miR‐203a‐3p could specifically bind to the 3′UTR of VEGFA and HIF‐1α. Over‐expression of VEGFA or HIF‐1α restored the tube formation activity of HRMECs suppressed by miR‐203a‐3p. In conclusion, our findings demonstrate that up‐regulation of miR‐203a‐3p might inhibit pathological retinal angiogenesis of PDR by targeting VEGFA and HIF‐1α. [ABSTRACT FROM AUTHOR]

Abstract Background miR-203a-3p was reported as a tumor suppressor and disregulated in many malignancies including nasopharyngeal carcinoma (NPC). However, its function in tumor growth and metastasis in NPC has rarely been reported. Methods The expression level of miR-203a-3p in human NPC tissues and cell lines was detected via real-time PCR (RT-PCR). Cell proliferation, migration and invasion were assessed in vitro by MTT, colony formation and transwell assay, respectively. The function of miR-203a-3p in vivo was detected through NPC xenograft tumor growth and lung metastatic mice model. Dual-luciferase reporter assay was used to identify the direct target of miR-203a-3p. Results The expression of miR-203a-3p was decreased in NPC tissues and cell lines in comparison with normal nasopharyngeal tissues and cell line. Ectopic expression of miR-203a-3p inhibited while inhibiting miR-203a-3p expression increased NPC cell proliferation, migration and invasion in vitro. MR-203a-3p overexpression suppressed xenograft tumor growth and lung metastasis in vivo. LASP1 was identified as a direct target of miR-203a-3p, which was confirmed by real-time PCR and western blotting assay. Ectopic expression of LASP1 partially reversed miR-203a-3p-mediated inhibition on proliferation, migration and invasion in NPC cells. Conclusion Collectively, miR-203a-3p suppresses tumor growth and metastasis through targeting LASP1 in NPC. The newly identified miR-203a-3p/LASP1 pathway provides further insights into the initiation and progression of NPC, which may represent a novel therapeutic target for NPC.

• Exosomal miR-203a-3p down-regulates the PTEN-activated AKT signalling pathway. • Secretion of CXCL12 by M2 macrophages promotes colorectal cancer cell development. • CXCL12 forms a positive feedback loop with miR-203a-3p. • miR-203a-3p is expected to be a biomarker for non-invasive liquid biopsy. (1) Background: Tumor-associated macrophages (TAMs) are important immunocytes associated with liver metastasis of colorectal cancer (CRLM). However, the molecular processes underpinning the interaction between the TME and the tumour-derived exosomal miRNAs in CRLM are not being fully understood; (2) Methods: Transmission electron microscopy was utilized to confirm the existence of exosomes after differential ultracentrifugation. To determine the roles of exosomal miR-203a-3p, an in vivo and in vitro investigation was conducted. The mechanism by which exosomal miR-203a-3p governs the interaction between CRC cells and M2 macrophages was investigated using a dual-luciferase reporter assay, western blot, and other techniques; (3) Results: Overexpression of miR-203a-3p was associated with poor prognosis and liver metastasis in CRC patients. Exosomal miR-203a-3p was upregulated in the plasma of CRC patients and highly metastatic CRC cells HCT116, and it could be transported to macrophages via exosomes. Exosomal miR-203a-3p induced M2 polarization of macrophages by controlling PTEN and activating the PI3K/Akt signaling pathway. M2-polarized macrophages secreted the CXCL12, which increased cancer metastasis and resulted in pre-metastatic niches in CRLM by CXCL12/CXCR4/NF-κB signaling pathway. Co-culture of macrophages with miR-203a-3p-transfected or exosome-treated cells increased the ability of HCT116 cells to metastasize both in vitro and in vivo; (4) Conclusions: Exosomes produced by highly metastatic CRC cells and rich in miR-203a-3p may target PTEN and alter the TME, promoting liver metastasis in CRC patients. These findings offer fresh understanding of the liver metastatic process in CRC. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is a degenerative joint disease that imposes a significant socioeconomic burden worldwide. Our previous studies revealed a down-regulation of miR-203a-3p in the knee tissues of OA patients. However, the underlying mechanism through which miR-203a-3p mediates the pathological process of OA remains unknown. Thus, we aimed to determine the effects of miR-203a-3p in the progression of OA., Methods: Rat primary chondrocytes were stimulated with 10 μg/mL lipopolysaccharide (LPS) for 24 hours, followed by transfection with 50 nM miR-203a-3p mimic, inhibitor, and siRNA for MYD88 or consistent negative controls for 48 hours. To evaluate the effects of miR-203a-3p on cartilage matrix degradation, oxidative stress, apoptosis, and pyroptosis in chondrocytes, various techniques such as immunofluorescence staining, biochemical analysis, Western blotting, and the TUNEL staining were utilized. In the rat OA model, all rats were randomly divided into four groups: Sham, OA, OA+Agomir negative control (NC), and OA+Agomir. They received intra-articular injections of 25 nmol miR-203a-3p agomir, agomir NC, or normal saline twice a week for the duration of 8 weeks after OA induction. Immunofluorescence staining was performed to evaluate the effects of miR-203a-3p on cartilage matrix degradation in rats., Results: MiR-203a-3p was down-regulated in LPS-treated rat chondrocytes and OA cartilage, and directly targeted MYD88. Moreover, miR-203a-3p significantly inhibited LPS-induced cartilage matrix degradation, oxidative stress, apoptosis, and pyroptosis of chondrocytes via targeting MYD88. Mechanistically, miR-203a-3p exerted protective effects via the inhibition of the MYD88/NF-κB pathway. In the rat OA model, intra-articular injections of miR-203a-3p agomir also significantly inhibited cartilage matrix degradation, thereby alleviating OA progression. Furthermore, the miR-203a-3p agomir-treated arthritic rat dramatically exhibited better articular tissue morphology and lower OARSI scores., Conclusions: MiR-203a-3p plays a role in alleviating the progression of OA by regulating the MYD88/NF-κB pathway, thereby inhibiting cartilage matrix degradation, oxidative stress, apoptosis, and pyroptosis of chondrocytes. It highlights the potential significance of miR-203a-3p as an important regulator of OA.

OBJECTIVE: Non-small cell lung cancer (NSCLC) is the main form of lung cancer, leading to major causes of cancer mortality. It is well known that lncRNAs may be involved in the pathogenesis of cancer, including NSCLC. The aim of this study was to provide a novel therapeutic target of LINC00342 for the therapy of NSCLC. PATIENTS AND METHODS: The expression of LINC00342 and miR-203a-3p was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Cell proliferation was measured using the MTT assay. Colony formation analysis was performed to count the number of colonies. Cell migration and invasion were measured by transwell. Online software DIANA tools were used to predict binding sites of LINC00342 and miR-203a-3p. Luciferase reporter assay was conducted to confirm the interaction between LINC00342 and miR-203a-3p. RESULTS: The expression of LINC00342 was increased in NSCLC tissues and cells compared with normal tissues and cells. Knockdown of LINC00342 suppressed cell proliferation, colony formation, migration, and invasion. LINC00342 regulated the expression of miR-203a-3p by targeting it directly. MiR-203a-3p was down-regulated in NSCLC tissues and cells compared with normal tissues and cells. Furthermore, LINC00342 promoted NSCLC cells proliferation, colony formation, migration, and invasion by depleting the expression of miR-203a-3p. CONCLUSIONS: This work implied that LINC00342 functions in NSCLC acting as an oncogene. Briefly, LINC00342 contributes to NSCLC cells growth and metastasis via targeting miR-203a-3p competitively. [ABSTRACT FROM AUTHOR]

Background: Earlier diagnosis is beneficial for the prognosis of hepatocellular carcinoma (HCC). Alpha fetoprotein (AFP) is the most widely used biomarker for HCC, but its sensitivity and specificity are only 60 and 90%, respectively. Therefore, it is of great clinical significance to identify early prognostic biomarkers for HCC, especially a blood-based biomarker as it offers several advantages over tissue-based biomarkers. Trefoil factor 3 (TFF3), a novel secretory protein, was over-expressed in HCC tissues, indicating it might be a blood-based biomarker for HCC. In addition, circulating microRNAs have been investigated as biomarkers for HCC, indicating that miR-7-5p and miR-203a-3p, which are reported or predicted to target TFF3, also hold promise as blood-based biomarkers for HCC.Methods: We enrolled 43 patients who were firstly diagnosed HCC and matched 47 control subjects without HCC. The levels of TFF3, miR-7-5p and miR-203a-3p were tested in the plasma of HCC patients. Moreover, we assayed the correlation of TFF3 with its related micro RNAs, miR-7-5p and miR-203a-3p, and evaluated their predictive powers for HCC.Results: Decrease of TFF3 was associated with increase of miR-203a-3p in the plasma of HCC patients and they displayed potent predictive powers for HCC diagnosis. However, there was no significant change of plasma miR-7-5p between HCC and control group.Conclusion: Decrease of TFF3 correlated with increase of miR-203a-3p in the plasma of HCC patients and they could be additional biomarkers to improve sensitivity and specificity in the diagnosis of HCC. [ABSTRACT FROM AUTHOR]

Soft tissue sarcoma (STS) is a heterogeneous group of rare malignancies with a five-year survival rate of approximately 50%. Reliable molecular markers for risk stratification and subsequent therapy management are still needed. Therefore, we analyzed the prognostic potential of miR-155-5p and miR-203a-3p expression in a cohort of 79 STS patients. MiR-155-5p and miR-203a-3p expression was measured from tumor total RNA by qPCR and correlated with the demographic, clinicopathological, and prognostic data of the patients. Elevated miR-155-5p expression was significantly associated with increased tumor stage and hypoxia-associated mRNA/protein expression. High miR-155-5p expression and low miR-203a-3p expression, as well as a combination of high miR-155-5p and low miR-203a-3p expression, were significantly associated with poor disease-specific survival in STS patients in the Kaplan–Meier survival analyses (p = 0.027, p = 0.001 and p = 0.0003, respectively) and in the univariate Cox regression analyses (RR = 1.96; p = 0.031; RR = 2.59; p = 0.002 and RR = 4.76; p = 0.001, respectively), but not in the multivariate Cox regression analyses. In conclusion, the oncomiR miR-155-5p and the tumor suppressor-miR miR-203a-3p exhibit an association with STS patient prognosis and are suggested as candidates for risk assessment.

Inflammatory breast cancer (IBC) is a rare yet aggressive breast cancer variant, associated with a poor prognosis. The major challenge for IBC is misdiagnosis due to the lack of molecular biomarkers. We profiled dysregulated expression of microRNAs (miRNAs) in primary samples of IBC and non-IBC tumors using human breast cancer miRNA PCR array. We discovered that 28 miRNAs were dysregulated (10 were upregulated, while 18 were underexpressed) in IBC vs. non-IBC tumors. We identified 128 hub genes, which are putative targets of the differentially expressed miRNAs and modulate important cancer biological processes. Furthermore, our qPCR analysis independently verified a significantly upregulated expression of miR-181b-5p, whereas a significant downregulation of miR-200b-3p, miR-200c-3p, and miR-203a-3p was detected in IBC tumors. Receiver operating characteristic (ROC) curves implied that the four miRNAs individually had a diagnostic accuracy in discriminating patients with IBC from non-IBC and that miR-203a-3p had the highest diagnostic value with an AUC of 0.821. Interestingly, a combination of miR-181b-5p, miR-200b-3p, and miR-200c-3p robustly improved the diagnostic accuracy, with an area under the curve (AUC) of 0.897. Intriguingly, qPCR revealed that the expression of zinc finger E box-binding homeobox 2 (ZEB2) mRNA, the putative target of miR-200b-3p, miR-200c-3p, and miR-203a-3p, was upregulated in IBC tumors. Overall, this study identified a set of miRNAs serving as potential biomarkers with diagnostic relevance for IBC.

Existing data suggest that proton pump inhibitors (PPIs), particularly omeprazole, have significant anti-tumor action in monotherapy and or combination chemotherapy. Hedgehog (Hh) signaling pathway represents a leading candidate as a molecular mediator of Barrett’s esophagus (BE). Studies have indicated reduced miRNAs in BE progression, however, little is known about the latent anti-neoplasm effects of miRNAs in BE cells. Here, we investigated whether omeprazole could inhibit BE progression by regulating Hh pathway and explored the promising Hh-targeted miRNAs in BE cells. We conducted qRT-PCR and immunoblotting assay to evaluate the effects of omeprazole on the expression of Hh signaling components and miR-203a-3p in CP-A and CP-B cells. The promising target genes of miR-203a-3p were predicted by bioinformatics methods, and verified by luciferase assays and qRT-PCR. The effects of omeprazole on BE cell proliferation and cell cycle distribution were determined. The overexpression or silencing of miR-203a-3p was performed to test its anti-proliferative effects. Finally, rescue experiments that miR-203a-3p inhibitor alleviated the effects of omeprazole on decreasing the levels of Gli1 mRNA, protein and luciferase were performed. Mechanistic studies showed that omeprazole could inhibit the expression of Gli1 and the nuclear localization of Gli1. Moreover, we determined that omeprazole could selectively up-regulated the expression of miR-203a-3p, and Gli1 was a bona fide target of miR-203a-3p. miR-203a-3p inhibitor alleviated the suppressing effects of omeprazole on Gli1 luciferase activity, mRNA and protein level. The functional assay suggested that omeprazole could dose-dependently inhibit BE cell growth and induce cell cycle arrest in G0/G1 phase. Additionally, overexpression and silencing of miR-203a-3p in BE cells disrupted cell cycle progress, resulting in suppressing and accelerating cell proliferation, respectively. Taken together, these data provide a novel mechanism of potentially anti-neoplastic effects for omeprazole through modulation of miR-203a-3p expression and thus suppressing Hh/Gli1 signaling in BE cells.

Existing data suggest that proton pump inhibitors (PPIs), particularly omeprazole, have significant anti-tumor action in monotherapy and or combination chemotherapy. Hedgehog (Hh) signaling pathway represents a leading candidate as a molecular mediator of Barrett's esophagus (BE). Studies have indicated reduced miRNAs in BE progression, however, little is known about the latent anti-neoplasm effects of miRNAs in BE cells. Here, we investigated whether omeprazole could inhibit BE progression by regulating Hh pathway and explored the promising Hh-targeted miRNAs in BE cells. We conducted qRT-PCR and immunoblotting assay to evaluate the effects of omeprazole on the expression of Hh signaling components and miR-203a-3p in CP-A and CP-B cells. The promising target genes of miR-203a-3p were predicted by bioinformatics methods, and verified by luciferase assays and qRT-PCR. The effects of omeprazole on BE cell proliferation and cell cycle distribution were determined. The overexpression or silencing of miR-203a-3p was performed to test its anti-proliferative effects. Finally, rescue experiments that miR-203a-3p inhibitor alleviated the effects of omeprazole on decreasing the levels of Gli1 mRNA, protein and luciferase were performed. Mechanistic studies showed that omeprazole could inhibit the expression of Gli1 and the nuclear localization of Gli1. Moreover, we determined that omeprazole could selectively up-regulated the expression of miR-203a-3p, and Gli1 was a bona fide target of miR-203a-3p. miR-203a-3p inhibitor alleviated the suppressing effects of omeprazole on Gli1 luciferase activity, mRNA and protein level. The functional assay suggested that omeprazole could dose-dependently inhibit BE cell growth and induce cell cycle arrest in G0/G1 phase. Additionally, overexpression and silencing of miR-203a-3p in BE cells disrupted cell cycle progress, resulting in suppressing and accelerating cell proliferation, respectively. Taken together, these data provide a novel mechanism of potentially anti-neoplastic effects for omeprazole through modulation of miR-203a-3p expression and thus suppressing Hh/Gli1 signaling in BE cells. [ABSTRACT FROM AUTHOR]

Sam68 was previously shown to be a critical host factor for foot-and-mouth disease virus (FMDV) replication. MicroRNA (miR) miR-203a is reportedly a negative regulator of Sam68 expression both in vitro and in vivo . Here, transfection of miR-203a-3p and miR-203a-5p mimics separately and in combination in a porcine cell line followed by FMDV infection resulted in diminished viral protein synthesis and a 4 and 6 log reduction in virus titers relative to negative controls, respectively. Unexpectedly, Sam68 expression was increased by miR-203a-5p transfection, but not miR-203a-3p. miR-203a-5p also down-regulated Survivin expression, which was predicted to play a role in FMDV infection. Moreover, miR-203a-5p but not miR-203a-3p affected a reduction in FMDV viral RNA. These effects were not replicated with a related Picornavirus, suggesting FMDV specificity. Importantly, miR-203a-3p and miR-203a-5p impaired FMDV infection across multiple FMDV serotypes. We concluded that miR-203a-3p and miR-203a-5p represent attractive potential naturally occurring bio-therapeutics against FMDV. [ABSTRACT FROM AUTHOR]

Our previous study demonstrated that microRNA-203a-3p (miR-203a-3p) was involved in the regulation of long non-coding RNA MEG8-mediated the progression of hemangioma, which is a benign tumor characterized by endothelial hyperplasia in the blood vessels and primarily occurring in infants and females. Therefore, the present study aimed to further investigate the effects of miR-203a-3p on endothelial cell proliferation, invasion and apoptosis, as well as its underlying mechanism in hemangioma. Human hemangioma endothelial cells (HemECs) were first transfected with either miR-203a-3p mimics or a miR-203a-3p inhibitor. Subsequently, vascular endothelial growth factor A (VEGFA) was overexpressed in these cells. Cell proliferation (by Cell Counting Kit-8 assay), apoptosis (by TUNEL assay), invasion (by Transwell assay) and PI3K/AKT signaling (by western blot) were assessed following transfection of these cells. Notably, transfection with miR-203a-3p mimics caused a reduction in cell proliferation, invasion and in the phosphorylation levels of PI3K and AKT, and promoted cell apoptosis in HemECs. By contrast, transfection with the miR-203a-3p inhibitor exerted the opposite effects compared with those of the miR-203a-3p mimics. miR-203a-3p was revealed to directly suppress VEGFA expression in HemECs. VEGFA overexpression alone increased cell proliferation and invasion, but decreased apoptosis. Furthermore, VEGFA co-transfection reversed the effects mediated by miR-203a-3p mimics transfection in HemECs. Mechanistically, miR-203a-3p was demonstrated to inactivate the PI3K/AKT pathway, whereas VEGFA overexpression produced the opposite effect. VEGFA co-transfection also attenuated the miR-203a-3p mimics-induced inactivation of PI3K/AKT signaling in HemECs. In conclusion, these data suggested that miR-203a-3p may inhibit endothelial cell proliferation and invasion, and promote apoptosis by inactivating VEGFA and PI3K/AKT signaling in hemangioma. These findings also implicated miR-203 as a possible treatment option for this disease. [ABSTRACT FROM AUTHOR]