MicroRNA-146a promotes gastric cancer cell apoptosis by targeting transforming growth factor β-activated kinase 1

نویسندگان

  • Yiming Chen
  • Bin Zhou
  • Lubai Xu
  • Hengwei Fan
  • Junqin Xie
  • Dan Wang
چکیده

Accumulating evidence suggests that microRNA (miR)-146a functions as an oncogene or tumor suppressor in various cancers. However, the role of miR‑146a in gastric cancer (GC) remains to be elucidated. The present study investigated the function of miR‑146a in GC cells. The results of the present study revealed that miR‑146a modulates GC cell apoptosis. Overexpression of miR‑146a significantly increased apoptosis of SGC‑7901 cells, whereas inhibition of miR‑146a protected cells from apoptosis. miR‑146a expression in GC cells was inversely correlated with transforming growth factor β‑activated kinase 1 (TAK1) expression, at the mRNA and protein levels. Furthermore, small interfering RNA‑mediated silencing of TAK1 enhanced GC cell apoptosis, whereas overexpression of TAK1 promoted survival of GC cells. Overexpression of miR‑146a or knockdown of TAK1 led to a marked increase in inhibitor of κBα (IκBα) and a decrease in B‑cell lymphoma 2 (Bcl‑2) expression levels in SGC‑7901 cells. By contrast, silencing of miR‑146a or TAK1 overexpression downregulated IκBα and upregulated Bcl‑2 expression levels. Therefore, the results of the present study demonstrated a novel negative feedback mechanism to promote GC cell apoptosis involving the miR‑146a/TAK1/nuclear factor-κB axis.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Effect of Transforming Growth Factor-β (TGF-β) on proliferation of gastric epithelial cells in culture

Objective: Helicobacter pylori has a well-established role in the development of gastric cancer. In vitro studies reveal increased proliferation of the gastric mucosa in the presence of H. pylori infection. It has been also shown that production of some cytokines, such as interleukin-1 beta (IL-1b) is in...

متن کامل

MicroRNA-146a-5p Limits Elevated TGF-β Signal during Cell Senescence

MicroRNAs (miRNAs) are small non-coding RNAs implicated in post-transcriptional suppression of target genes in a sequencespecific manner and are thereby able to modulate cellular processes. miR-146a seems to play multiple roles in terms of regulating different phenotypes by targeting a wide range of different genes in various cellular contexts. Notably, miR-146a-5p targets Smad4 and tumor necro...

متن کامل

The let-7g microRNA promotes follicular granulosa cell apoptosis by targeting transforming growth factor-β type 1 receptor.

The intronic microRNA let-7g controls cell differentiation and proliferation during angiogenesis and oncogenesis. Here, we demonstrate that let-7g regulates granulosa cell (GC) apoptosis and follicular atresia in the pig ovary. Bioinformatics analyses and luciferase reporter assays showed that transforming growth factor-β type 1 receptor (TGFBR1) is a let-7g target. Overexpression of let-7g ind...

متن کامل

Expression and function of transforming growth factor-β-activated protein kinase 1 in gastric cancer

The present study aimed to investigate the expression and role of transforming growth factor (TGF) ‑β‑activated protein kinase 1 (TAK1) in human gastric cancer. Immunohistochemistry was performed to investigate the expression of TAK1 in surgical specimens of human gastric cancer tissue and adjacent normal tissue. The association between TAK1 and clinicopathologic factors was analyzed and the as...

متن کامل

Upregulation of miR-146a increases cisplatin sensitivity of the non-small cell lung cancer A549 cell line by targeting JNK-2

The aim of the present study was to investigate the effects of microRNA (miR-)146a on the cisplatin sensitivity of the non-small cell lung cancer (NSCLC) A549 cell line and study the underlying molecular mechanism. The differences in expression of miRNAs between A549 and A549/cisplatin (A549/DDP) cells were determined, and miR-146a was selected to study its effect on cisplatin sensitivity of A5...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 16  شماره 

صفحات  -

تاریخ انتشار 2017