Aberrant high expression level of MORC2 is a common character in multiple cancers

Summary Microrchidia 2 (MORC2) plays important roles in DNA damage repair and lipogenesis, but the clinical and functional role of MORC2 in cancer remains largely unexplored. In this study, we showed that MORC2 was widely expressed in human tissues while significantly up-regulated in most cancer types employing immunohistochemical staining and analysis of mRNA expression profile of more than 2000 human tissue samples from 15 different organs (lung, prostate, liver, breast, brain, stomach, colon/rectum, pancreas, ovary, endometrium, skin, nasopharynx, kidney, oesophagus and bladder). We also found that the MORC2 expression level in high grade cancer tissues was much more elevated and associated with unfavorable pathological characteristics, poor overall survival and disease-free survival in several kinds of cancers such as non-small cell lung cancer (NSCL) and breast cancer. Gene set enrichment analysis (GSEA) was used to predict the genes modulated by MORC2 and the results showed that dysregulation of MORC2 in tumor may take part in the cell cycle regulation and genomic instability. We observed that MORC2 knockdown would arrest the cell cycle progress and the genome of tumors with high MORC2 expression contained more point mutations and gene copy number variation, which validates our GSEA results. The results also showed that MORC2 knockdown would significantly inhibit the proliferation, colony forming, migration and invasion in multiple cancer cell lines. Taken together, these results highlight the importance of MORC2 in tumorigenesis and cancer progression, and it may act as a potential diagnostic marker and therapeutic target for these diseases.