CMIP is oncogenic in human gastric cancer cells

Gastric cancer is one of the most common cancers and the second leading cause of cancer-associated mortality worldwide. Recurrence, metastasis and resistance to drug treatment are the main barrier to survival of patients with advanced stage gastric cancer. Further study of the molecular mechanisms involved will improve the therapeutic options for gastric cancer. In a previous study, c-Maf was discovered as an oncogene transduced in the avian AS42 retrovirus, and was found to be overexpressed in multiple myeloma and angioimmunoblastic T-cell lymphoma. c-Maf inducing protein (CMIP) is involved in the c-Maf signaling pathway, which was reported to serve an important role in human minimal change nephrotic syndrome and in human reading and language related behavior. However, the relationship between CMIP and human gastric cancer has not yet been reported. In the present study, CMIP protein levels in gastric cancer tissues and cells were measured using immunohistochemistry and western blot analysis; the expression of CMIP protein was significantly higher in gastric cancer tissues compared with normal gastric tissues. Expression was positively associated with poorer clinical parameters, relapse-free survival and overall survival. Furthermore, using cell counting, Cell Counting Kit-8, colony formation, wound healing and Transwell assays, together with flow cytometry, CMIP depletion by RNA interference was observed to reduce the capacity of gastric cancer cells to proliferate and migrate in vitro. Furthermore, the upstream and downstream genes of CMIP were analyzed by luciferase reporter assay and reverse transcription quantitative polymerase chain reaction, which indicated that CMIP was a direct target of miR-101-3p. In addition, CMIP knockdown was observed to result in the downregulation of MDM2 and mitogen activated protein kinase (MAPK) expression at the mRNA level. In conclusion, CMIP demonstrated an oncogenic role in human gastric cancer cells. Furthermore, microRNA-101-3p, MDM2 and MAPK were involved in the CMIP signaling pathway in gastric cancer. CMIP could be a novel target for further investigation in the clinical therapeutic management of gastric cancer.