Abstract
BackgroundTransmembrane protein 158 (TMEM158) is a recently identified upregulated gene during Ras-induced senescence. Its association with various cancers has been recently reported. However, the expression and biological function of TMEM158 in ovarian cancer is still unclear. This study was aimed to elucidate the roles of TMEM158 in cell proliferation, adhesion and cell invasion of ovarian cancer cells.MethodsWe analyzed TMEM158 mRNA level in ovarian cancer tissues and adjacent no-tumorous tissues by real-time PCR. We then suppressed TMEM158 expression of ovarian cancer cells by RNA interference and examined the effects of TMEM158 knockdown on cancerous transformation of ovarian cancer cells.ResultsThe RNA-sequencing data of the ovarian cancer cohort from The Cancer Genome Atlas project (TCGA) and our real-time PCR data showed that TMEM158 was overexpressed in ovarian cancer. Knockdown of TMEM158 by RNA interference in ovarian cancer cells significantly inhibited cell proliferation, which may be due to the increase of G1-phase arrest. Silencing of TMEM158 also inhibited cell adhesion, cell invasion as well as tumorigenicity in nude mice. Moreover, knockdown of TMEM158 notably repressed cell adhesion via down-regulating the expression intercellular adhesion molecule1 (ICAM1) and vascular cell adhesion molecule1 (VCAM1). Transforming Growth Factor-β (TGF-β) signaling pathway was also remarkably impaired by TMEM158 silencing.ConclusionsOur data suggests that TMEM158 may work as an oncogene for ovarian cancer and that inhibition of TMEM158 may be a therapeutic strategy for ovarian cancer.
Highlights
Ovarian cancer is the most lethal type of gynecologic malignancy [1]
Transmembrane protein 158 (TMEM158) was overexpressed in ovarian cancer To explore the expression of TMEM158 in ovarian cancer, we compared its expression by analyzing high throughput RNA-sequencing data of the ovarian cancer cohort from The Cancer Genome Atlas project (TCGA, https://tcga-data.nci.nih.gov/tcga/)
An overexpression of TMEM158 was found in 84 % (21/25) of tested ovarian cancer tissues (Fig. 1b)
Summary
Ovarian cancer is the most lethal type of gynecologic malignancy [1]. Due to its insidious onset, ovarian cancer is often diagnosed in advanced stages, resulting in a poor survival rate [2]. The five-year survival of patients with ovarian cancer is almost 30 % and has not significantly changed over the past 30 years regardless of important advances in surgery, radiation and chemotherapy [3,4,5,6,7]. This emphasizes the need for new diagnosis markers and therapies based on a well understanding of the molecular mechanisms underlying the oncogenesis and development of ovarian cancer. Transmembrane protein 158 (TMEM158) is a recently identified upregulated gene during Ras-induced senescence. This study was aimed to elucidate the roles of TMEM158 in cell proliferation, adhesion and cell invasion of ovarian cancer cells
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