Silencing of TMEM158 Inhibits Tumorigenesis and Multidrug Resistance in Colorectal Cancer

Abstract

Transmembrane protein 158 (TMEM158) plays pivotal roles in many cancers, including colorectal cancer (CRC). It has been reported that it is a recently identified upregulated gene during Ras-induced senescence. However, the clinical significance and biological functions of TMEM158 in CRC remain largely unknown. In this study, we found that TMEM158 was highly expressed in CRC tissues and cell lines compared with the corresponding noncancerous samples and normal colon epithelial cells. In vitro studies showed that TMEM158 silencing inhibited proliferation, and migration and increased apoptosis of CRC cells, whereas overexpression of TMEM158 increased proliferation, migration, and apoptosis escape of CRC cells. Mechanically, the levels of drug resistance-associated molecules, including multidrug resistance 1 and multidrug resistance protein 1, as well as the expression of antiapoptotic Bcl-2 were significantly upregulated. In addition, TMEM158 knockdown significantly inhibited tumor growth in vivo. Collectively, these results demonstrated that TMEM158 is a significant regulator of tumorigenesis and drug resistance in CRC and provided evidence that TMEM158 may be a promising target for CRC therapy.

Disclosure Statement

The authors declare no conflict of interest.

Authors' Contributions

Lihua Liu, Jiantao Zhang and Jiandong Tai designed the study, carried out the experiments and drafted the manuscript; Lihua Liu, Jiantao Zhang, LiBin Yin, Shiquan Li, and Jiandong Tai participated in the experiments and data analysis. All authors read and approved the final manuscript. Lihua Liu, Jiantao Zhang contributed equally to this work.

Additional information

Funding

This work was Applied Health Research Project of Jilin Provincial Finance Department (No. 3D516C053428).