Department of Colorectal and Anal Surgery, The First Hospital of Jilin University, Changchun, China.
Nutr Cancer. 2020;72(4):662-671. doi: 10.1080/01635581.2019.1650192. Epub 2019 Aug 7.
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.
跨膜蛋白 158（TMEM158）在多种癌症中发挥着关键作用，包括结直肠癌（CRC）。有报道称，它是 Ras 诱导衰老过程中最近发现的一个上调基因。然而，TMEM158 在 CRC 中的临床意义和生物学功能仍知之甚少。在本研究中，我们发现与相应的非癌样本和正常结肠上皮细胞相比，TMEM158 在 CRC 组织和细胞系中高表达。体外研究表明，TMEM158 沉默抑制 CRC 细胞的增殖、迁移和凋亡，而过表达 TMEM158 则增加 CRC 细胞的增殖、迁移和凋亡逃逸。机制上，耐药相关分子的水平，包括多药耐药蛋白 1 和多药耐药 1，以及抗凋亡 Bcl-2 的表达均显著上调。此外，TMEM158 敲低显著抑制体内肿瘤生长。综上所述，这些结果表明 TMEM158 是 CRC 发生和耐药的重要调节因子，并为 TMEM158 可能成为 CRC 治疗的有前途的靶点提供了证据。
