Behavior Of Colon Cancer Cells Research Articles

RETRACTED: MicroRNA-498 disturbs the occurrence and aggression of colon cancer through targeting MDM2 to mediate PPARγ ubiquitination

MicroRNA (miR)-498 is indicative of diagnostic and prognostic significance in colon cancer (CC). On the basis of that, this study is initiated from miR-498, combined with mouse double minute 2 (MDM2)/peroxisome proliferator-activated receptor γ (PPARγ) ubiquitination axis to have an insight into CC progression. CC tissues and their adjacent tissues were harvested to determine miR-498, MDM2 and PPARγ expression. The interactions among these three factors were identified. The screened human CC cells were transfected with miR-498/MDM2-related sequences, followed by detection of the biological behaviors of CC cells. Xenografted tumors were taken to validate cell experimental outcomes. Bioinformatics and dual-luciferase report analysis verified the targeting relationship between miR-498 and MDM2. The relation between MDM2 and PPARγ was identified by immunoprecipitation and in vivo deubiquitination. Down-regulated miR-498 and PPARγ and up-regulated MDM2 were exhibited in CC. miR-498 targeted MDM2 while MDM2 mediated PPARγ ubiquitination. Elevated miR-498 or reduced MDM2 impaired cell viability, colony-forming, migratory and invasive activities and enhanced apoptosis in CC. Elevated MDM2 abolished the effects of up-regulated miR-498 on the biological behaviors of CC cells. Elevated miR-498 or reduced MDM2 depressed tumorigenic ability of CC cells in mice. It is conclusive that restoring miR-498 depresses MDM2 to modify PPARγ ubiquitination, thereby disturbing the tumorigenesis of CC. This work constructs the base for exploring novel agents in treating CC.

Roles of DANCR/microRNA-518a-3p/MDMA ceRNA network in the growth and malignant behaviors of colon cancer cells

BackgroundThe competing endogenous RNA (ceRNA) networks of long non-coding RNAs (lncRNAs) and microRNAs (miRs) have aroused wide concerns. The study aims to investigate the roles of lncRNA DANCR-associated ceRNA network in the growth and behaviors of colon cancer (CC) cells.MethodsDifferentially expressed lncRNAs between CC and paracancerous tissues were analyzed using microarrays and RT-qPCR. Follow-up studies were conducted to evaluate the correlation between DANCR expression and prognosis of CC patients. Loss-of-functions of DANCR were performed to identify its role in the malignant behaviors of CC cells. Sub-cellular localization of DANCR and the potential targets of DANCR were predicted and validated. Cells with inhibited DANCR were implanted into nude mice to evaluate the tumor formation and metastasis in vivo.ResultsDANCR was highly-expressed in CC tissues and cell lines, and higher levels of DANCR were linked with worse prognosis and less survival time of CC patients. Silencing of DANCR inhibited proliferation, viability, metastasis and resistance to death of CC cells. DANCR was found to be sub-localized in cytoplasmic matrix and to mediate murine double minute 2 (MDM2) expression through sponging miR-518a-3p in CC cells, during which the Smad2/3 signaling was activated. Likewise, silencing of DANCR in CC cells inhibited tumor formation and metastasis in vivo.ConclusionThis study provided evidence that silencing of DANCR might inhibit the growth and metastasis of CC cells through the DANCR/miR-518a-3p/MDM2 ceRNA network and the defect of Smad2/3 while activation of the p53 signaling pathways. This study may offer novel insights in CC treatment.

Effects of long non-coding RNA Opa-interacting protein 5 antisense RNA 1 on colon cancer cell resistance to oxaliplatin and its regulation of microRNA-137.

BACKGROUNDThe incidence of colon cancer (CC) is currently high, and is mainly treated with chemotherapy. Oxaliplatin (L-OHP) is a commonly used drug in chemotherapy; however, long-term use can induce drug resistance and seriously affect the prognosis of patients. Therefore, this study investigated the mechanism of Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) on L-OHP resistance by determining the expression of OIP5-AS1 and microRNA-137 (miR-137) in CC cells and the effects on L-OHP resistance, with the goal of identifying new targets for the treatment of CC.AIMTo study the effects of long non-coding RNA OIP5-AS1 on L-OHP resistance in CC cell lines and its regulation of miR-137.METHODSA total of 114 CC patients admitted to China-Japan Union Hospital of Jilin University were enrolled, and the expression of miR-137 and OIP5-AS1 in tumor tissues and corresponding normal tumor-adjacent tissues was determined. The influence of OIP5-AS1 and miR-137 on the biological behavior of CC cells was evaluated. Resistance to L-OHP was induced in CC cells, and their activity was determined and evaluated using cell counting kit-8. Flow cytometry was used to analyze the apoptosis rate, Western blot to determine the levels of apoptosis-related proteins, and dual luciferase reporter assay combined with RNA-binding protein immunoprecipitation to analyze the relationship between OIP5-AS1 and miR-137.RESULTSOIP5-AS1 was up-regulated in CC tissues and cells, while miR-137 was down-regulated in CC tissues and cells. OIP5-AS1 was inversely correlated with miR-137 (P < 0.001). Silencing OIP5-AS1 expression significantly hindered the proliferation, invasion and migration abilities of CC cells and markedly increased the apoptosis rate. Up-regulation of miR-137 expression also suppressed these abilities in CC cells and increased the apoptosis rate. Moreover, silencing OIP5-AS1 and up-regulating miR-137 expression significantly intensified growth inhibition of drug-resistant CC cells and improved the sensitivity of CC cells to L-OHP. OIP5-AS1 targetedly inhibited miR-137 expression, and silencing OIP5-AS1 reversed the resistance of CC cells to L-OHP by promoting the expression of miR-137.CONCLUSIONHighly expressed in CC, OIP5-AS1 can affect the biological behavior of CC cells, and can also regulate the resistance of CC cells to L-OHP by mediating miR-137 expression.