Overexpression of TMEM158 contributes to ovarian carcinogenesis.
Overexpression of TMEM158 contributes to ovarian carcinogenesis.
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TMEM158的过表达有助于卵巢癌发生。
DOI：
10.1186/s13046-015-0193-y
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发表时间：
2015-08-04
期刊：
影响因子：
--
通讯作者：
Qu X
中科院分区：
文献类型：
--
作者：
Cheng Z;Guo J;Chen L;Luo N;Yang W;Qu X
跨膜蛋白158 （TMEM158）是最近发现的在ras诱导的衰老过程中上调的基因。它与各种癌症的关系最近得到了报道。然而，TMEM158在卵巢癌中的表达及其生物学功能尚不清楚。本研究旨在阐明TMEM158在卵巢癌细胞增殖、粘附和细胞侵袭中的作用。我们通过实时荧光定量PCR分析了TMEM158 mRNA在卵巢癌组织和癌旁非肿瘤组织中的表达水平。然后，我们通过RNA干扰抑制卵巢癌细胞的TMEM158表达，并检测TMEM158敲除对卵巢癌细胞癌变的影响。来自The cancer Genome Atlas project （TCGA）的卵巢癌队列rna测序数据和我们的real-time PCR数据显示，TMEM158在卵巢癌中过表达。在卵巢癌细胞中，RNA干扰敲低TMEM158可显著抑制细胞增殖，这可能与g1期阻滞增加有关。TMEM158的沉默也抑制了裸鼠的细胞粘附、细胞侵袭和致瘤性。此外，敲低TMEM158通过下调细胞间粘附分子1 （ICAM1）和血管细胞粘附分子1 （VCAM1）的表达显著抑制细胞粘附。TMEM158沉默也显著损害了转化生长因子-β (TGF-β)信号通路。我们的数据表明，TMEM158可能是卵巢癌的致癌基因，抑制TMEM158可能是卵巢癌的一种治疗策略。
Transmembrane 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. We 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. The 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. Our 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.