miR-1307-3p overexpression inhibits cell proliferation and promotes cell apoptosis by targeting ISM1 in colon cancer.

colon adenocarcinoma (COAD) is the most common malignant tumor of gastrointestinal tract. Our study attempts to explore the effect of miR-1307-3p on biological function of COAD cells and its connection with isthmin 1 (ISM1). The miRNA dataset and clinical information of patients with COAD were downloaded from The Cancer Genome Atlas (TCGA) database. The survival prognosis was analyzed by GGSURV package from R. MicroRNA (miR)-1307-3p was identified by identifying overlapping miRNAs that target ISM1, across two databases (miRDB and Targetscan). Dual luciferase reporter assay was employed to scrutinize the relationship between miR-1307-3p and ISM1. RT-PCR was used to quantify miR-1307-3p and ISM1 expression of colon cancer tissues and cell lines. Western blot was performed to quantify related protein expression. Flow Cytometry, CCK8 and colony formation assays were performed to evaluate the apoptosis, cell cycle, cell viability and proliferation of COAD cells. miR-1307-3p mRNA level decreased in both COAD tissues and cell lines. Overexpression of miR-1307-3p suppressed the proliferation, promoted apoptosis and arrested cell cycle at G1 phase, meanwhile, downregulation of ISM1 accelerated the proliferation, inhibited apoptosis and promote cell cycleprogression. The result of dual luciferase reporter assay indicated that miR-1307-3p targeted ISM1 directly and inhibited its expression. The functions of miR-1307-3p regulating cleaved caspase-3, cyclinD1, Ki67 protein levels and activation of Wnt3a/β-catenin signaling pathway were reversed by ISM1. miR-1307-3p inhibited activation of Wnt3a/β-catenin signaling through targeting downregulation of ISM1, thereby inhibited proliferation and promote apoptosis of COAD cells.

Zheng Y ，Zheng Y ，Lei W ，Xiang L ，Chen M ... -  《-》

LINC00342 regulates cell proliferation, apoptosis, migration and invasion in colon adenocarcinoma via miR-545-5p/MDM2 axis.

Colon adenocarcinoma (COAD) is the third most common cancer in the world. We aimed to explore the functional mechanism of LINC00342 in COAD. The LINC00342 expressions in COAD tissues were detected via qRT-PCR and in situ hybridization analysis. Statistical analysis was performed to analyze the relationship between LINC00342 expression and COAD clinical features. Small interfering LINC00342 (siLINC00342)/siCtrl were synthesized and then transfected into COAD cells. Cell apoptosis and proliferation were respectively assessed by flow cytometry and cell counting kit-8 assay. Cell migration and invasion were both measured using transwell assay. The target miRNA of LINC00342 were predicted and verified by online bioinformatics tools and luciferase reporter assay and RNA pull-down assay. Mice COAD models were constructed to explore the effects of LINC00342 on COAD in vivo. LINC00342 was over-expressed in COAD tissues and LINC00342 overexpression was related to the poor prognosis of COAD patients. LINC00342 knockdown inhibited cell proliferation, migration and invasion and promoted apoptosis of COAD cells. LINC00342 targeted to miR-545-5p/murine double minute 2 (MDM2) in COAD. In COAD tissues and cell lines, LINC00342 expression was positively correlated to MDM2 expression, while it was negatively correlated to miR-545-5p expression. Both miR-545-5p-mimic and siMDM2 transfection could recover the changes of cell biological activities which were induced by LINC00342 overexpression. LINC00342 knockdown suppressed COAD tumor growth in vivo. LINC00342 affected cell biological activities of COAD in vivo and in vitro via regulating miR-545-5p/MDM2. It might a novel target in COAD therapy.

Miao Z ，Liu S ，Xiao X ，Li D ... -  《-》

miR-1184 regulates the proliferation and apoptosis of colon cancer cells via targeting CSNK2A1.

MicroRNA (miRNA) exerts an important part in colon cancer cell proliferation and apoptosis. Meanwhile, the dysregulation of some miRNAs is detected in colon cancer cells. However, it remains unclear about the underlying mechanism of their effects on tumor pathogenesis. The current work aimed to examine the miR-1184 effect on colon cancer cells. The differentially expressed miRNAs (DEMs), including miR-9-3p, miR-1184, miR-492, miR-92a-1-5p and miR-20a-3p, were obtained from the GSE115108 and GSE132619 data sets using the 'GEO2R' online tool. Based on the findings, miR-1184 was significantly down-regulated within colon cancer cells and tissues. Moreover, the experimental results of CCK8, flow cytometry, colony formation and Western blotting assays showed that, miR-1184 over-expression suppressed colon cancer cell proliferation through inhibiting Ki67 expression and promoted their apoptosis through up-regulating cleaved caspase-3 and down-regulating Bcl-2 expression. By contrast, miR-1184 inhibition exerted the opposite effects. A total of 110 target genes of miR-1184 were predicted using the TargetScan and miRTarBase databases, which were then used to construct the protein-protein interaction (PPI) network based on the DAVID and STRING websites and to perform GO and KEGG pathway enrichment analyses. The MCODE plug-in of cytoscape was utilized to verify that CSNK2A1 was the target gene and key gene in significant modules. MiR-1184 directly targets CSNK2A1 via using RNA immunoprecipitation assay and luciferase reporter gene assay. According to the results, CSNK2A1 over-expression reversed the functions of miR-1184 over-expression in suppressing colon cancer cell proliferation and enhancing their apoptosis. In conclusion, over-expression of miR-1184 inhibits colon cancer cell proliferation but promotes their apoptosis through down-regulating CSNK2A1 expression.

Chen S ，Wang Y ，Xu M ，Zhang L ，Su Y ，Wang B ，Zhang X ... -  《-》

miR-101-3p and miR-199b-5p promote cell apoptosis in oral cancer by targeting BICC1.

microRNAs (miRNAs) are involved in the carcinogenesis and progression of oral cancer. In this research, we aimed to identify the DE_miRNAs in oral cancer and the related molecular mechanisms. Using the GEO2R online tool, we identified 19 DE_miRNAs from the GSE115117 dataset and 3343 the DEGs from GSE74530 dataset. GO enrichment analysis of DE_miRNAs were performed using FunRich online analysis. Venn diagrams of the overlapping genes regulated by miR-204-5p, miR-199b-5p, and miR-101-3p were constructed using Draw Venn Diagram, FunRich, miRDB, TargetScan and GSE74530 databases. Cytoscape was used to construct a miRNAs-mRNAs network. RT-PCR and western blotting showed downregulation of miR-199b-5p and miR-101-3p, and upregulation of BICC1 in oral cancer cell lines and tissues. Spearman correlation analysis further demonstrated a positive correlation between miR-101-3p and miR-199b-5p levels and that miR-199b-5p and miR-101-3p were negatively correlated with BICC1 mRNA levels. miR-199b-5p and BICC1 were significantly related to survival rate of patients with oral cancer. Upregulation of miR-199b-5p and miR-101-3p inhibited the viability and promoted the apoptosis in TSCCA and SCC-9 cells, as shown by the CCK8 assay and flow cytometry analysis, respectively. Inhibition of BICC1 reduced viability and promoted apoptosis in TSCCA cells. Additionally, the relationship between BICC1 and both miR-101-3p and miR-199b-5p was assessed by a luciferase reporter assay. The effects of miR-101-3p and miR-199b-5p upregulation on the promotion of cell apoptosis and the inhibition of tumor growth were reversed by overexpression of BICC1. In conclusion, the increased levels of miR-199b-5p and miR-101-3p enhanced apoptosis and suppressed cell viability in oral cancer by suppressing BICC1 expression.

Wang H ，Guo Y ，Mi N ，Zhou L ... -  《-》

miR-590-3p promotes colon cancer cell proliferation via Wnt/β-catenin signaling pathway by inhibiting WIF1 and DKK1.

Feng ZY ，Xu XH ，Cen DZ ，Luo CY ，Wu SB ... -  《-》