Long non-coding RNA MDC1-AS inhibits human gastric cancer cell proliferation and metastasis through an MDC1-dependent mechanism

Exp Ther Med. 2018 Jan;15(1):191-197. doi: 10.3892/etm.2017.5370. Epub 2017 Oct 24.

Abstract

Gastric cancer is the third leading cause of cancer-associated mortality worldwide and is one of the most common malignancies in China. However, the molecular mechanisms underlying the tumorigenesis of gastric cancer remain largely unclear. Long non-coding (Lnc)RNAs have been demonstrated to serve significant roles in the tumorigenesis of various types of cancer. The present study aimed to explore the role of the LncRNA mediator of DNA damage checkpoint protein 1-antisense RNA (MDC1-AS), the antisense transcript of MDC1, in human gastric cancer. The results revealed that the expression of MDC1-AS in human gastric cancer was significantly suppressed in vivo and in vitro. In addition, overexpression of MDC1-AS in the poorly differentiated gastric cancer cell line MKN28 significantly inhibited cell proliferation and metastasis, while the knockdown of MDC1-AS in well-differentiated MKN45 gastric cancer cells significantly increased proliferation and metastasis. The knockdown of MDC1 relieved the inhibitory effect of MDC1-AS on MKN28 cell proliferation and metastasis, while the overexpression of MDC1 attenuated the stimulatory effect of MDC1-AS knockdown in MKN45 cells. Thus, the present study demonstrated that MDC1-AS had an inhibitory on gastric tumorigenesis through an MDC1-dependent mechanism. This indicates that MDC1-AS is a potential novel therapeutic target for the diagnosis and treatment of human gastric cancer in the clinic.

Keywords: gastric cancer; long non-coding RNA; mediator of DNA damage checkpoint protein 1; mediator of DNA damage checkpoint protein 1-antisense RNA; metastasis; proliferation.