MiR-130a upregulates mTOR pathway by targeting TSC1 and is transactivated by NF-? B in high-grade serous ovarian carcinoma

Yuqiong Wang, Xiyu Zhang, Wei Tang, Zhenghong Lin, Limei Xu, Ruifen Dong, Yinuo Li, Jieyin Li, Zaixin Zhang, Xiangzhi Li, Ling Zhao, Jian Jun Wei, Changshun Shao, Beihua Kong, Zhaojian Liu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Activation of mammalian target of rapamycin (mTOR) signaling pathway is associated with poor prognosis of epithelial ovarian cancer. The TSC1-TSC2 complex is a critical negative regulator of mTOR signaling. Here, we demonstrated that TSC1 was frequently downregulated in high-grade serous ovarian carcinoma (HGSOC) and low TSC1 expression level is associated with advanced tumor stage. We next identified miR-130a to be a negative regulator of TSC1 by targeting its 3'UTR. miR-130a was overexpressed in HGSOC and could drive proliferation and invasion/metastasis of ovarian cancer cells. miR-130a could also attenuate rapamycin/starvation-induced autophagy. Ectopic TSC1 expression could block the effects of miR-130a on cell proliferation, migration and autophagy. Finally, we found that miR-130a expression could be upregulated by inflammatory factors and was transactivated by NF-? B. Therefore, our findings establish a crosstalk between inflammation and mTOR signaling that is mediated by miR-130a, which might have a pivotal role in the initiation and progression of HGSOC.

Original languageEnglish (US)
Pages (from-to)2089-2100
Number of pages12
JournalCell Death and Differentiation
Volume24
Issue number12
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'MiR-130a upregulates mTOR pathway by targeting TSC1 and is transactivated by NF-? B in high-grade serous ovarian carcinoma'. Together they form a unique fingerprint.

Cite this