miR-188-5p promotes oxaliplatin resistance by targeting RASA1 in colon cancer cells.

The efficacy of chemotherapy for colon cancer is limited due to the development of chemoresistance. MicroRNA (miR)-188-5p is downregulated in various types of cancer. The aim of the present study was to explore the molecular role of miR-188 in oxaliplatin (OXA) resistance. An OXA-resistant colon cancer cell line, SW480/OXA, was used to examine the effects of miR-188-5p on the sensitivity of colon cancer cells to OXA. The target of miR-188-5p was identified using a luciferase assay. Cell cycle distribution was also assessed using flow cytometry. The measurement of p21 protein expression, Hoechst 33342 staining and Annexin V/propidium iodide staining was used to evaluate apoptosis. The expression of miR-188-5p significantly increased in SW480/OXA compared with wild-type SW480 cells. The luciferase assay demonstrated that miR-188-5p inhibited Ras GTPase-activating protein 1 (RASA1; also known as p120/RasGAP) luciferase activity by binding to the 3'-untranslated region of RASA1 mRNA, suggesting that miR-188-5p could target RASA1. In addition, miR-188-5p downregulation or RASA1 overexpression promoted the chemosensitivity of SW480/OXA, as evidenced by increased apoptosis and G1/S cell cycle arrest. Moreover, RASA1 silencing abrogated the increase in cell apoptosis induced by the miR-188-5p inhibitor. The findings of the present study suggested that miR-188-5p could enhance colon cancer cell chemosensitivity by promoting the expression of RASA1.

Knockdown of PARP6 or survivin promotes cell apoptosis and inhibits cell invasion of colorectal adenocarcinoma cells.

Colorectal adenocarcinoma is the third most common cancer worldwide. PARP6, a novel member of the poly(ADP-ribose) polymerases (PARPs) and survivin, a member of the family of inhibitor of apoptosis (IAP) proteins are associated with a poor prognosis in various types of cancers. However, limited evidence exists regarding the interaction between PARP6 and survivin in colorectal adenocarcinoma. In the present study, we used the paired samples of 20 patients with colorectal adenocarcinoma to detect the expression of PARP6 and survivin in both tumor and adjacent normal colorectal mucosa. Their interaction and roles in cell viability, cell cycle, cell apoptosis and cell invasion were further investigated. Our results showed that both PARP6 and survivin exhibited higher expression in colorectal adenocarcinoma tissues and SW620 cells when compared with levels in adjacent non-tumor tissues and a normal colon cell line FHC. Co-immunoprecipitation assay showed that a significant correlation existed between PARP6 and survivin. We also showed that sole treatment of PARP6 siRNA or survivin siRNA partially inhibited the cell survival and invasion, induced cell G0/G1 arrest, and cell apoptosis at the early and late stages. The combined treatment of PARP6 siRNA and survivin siRNA suppressed the cell survival and cell invasion, further induced cell cycle phase G0/G1 arrest, and cell apoptosis at the early and late stages. Taken together, knockdown of PARP6 or survivin promotes cell apoptosis and inhibits the cell invasion of colorectal adenocarcinoma cells. A significant correlation exists between PARP6 and survivin, and both are promising targets for the development of new strategies for the diagnosis and treatment of advanced or metastatic colorectal adenocarcinoma.

Abrogation of MUC5AC Expression Contributes to the Apoptosis and Cell Cycle Arrest of Colon Cancer Cells.

Deregulated expressions of mucins have been found in various malignancies and play a pivotal role in carcinogenesis. MUC5AC, as a secreted mucin, is reported to be aberrantly expressed during epithelial cancer progression, including colon cancer. However, the mechanisms of the oncoprotein MUC5AC in the initiation of colon cancer requires further investigation. Here, we collected colon cancer tissues (n = 20) and corresponding paracancerous tissues (n = 20) and found that the expression of MUC5AC was significantly elevated in colon cancer tissues when compared with the corresponding paracancerous tissues. Immunofluorescence indicated that all colon cancer cell lines, including HT29, SW620, and the normal human intestinal epithelial cells FHC, showed the positive expression of MUC5AC, and SW620 exhibited the highest expression. Moreover, knockdown of MUC5AC in SW620 cells remarkably suppressed cell vitality and promoted apoptosis and G1 cell cycle arrest, resulting in the impaired ability of colony formation. Furthermore, the inhibition of MUC5AC in SW620 cells dramatically repressed the cell migration and invasion. These results demonstrated that MUC5AC as an oncogene could be a promising target in the treatment of colon cancer.