PMID- 28800130 OWN - NLM STAT- MEDLINE DCOM- 20180725 LR - 20220330 IS - 1476-5403 (Electronic) IS - 1350-9047 (Print) IS - 1350-9047 (Linking) VI - 24 IP - 12 DP - 2017 Dec TI - miR-130a upregulates mTOR pathway by targeting TSC1 and is transactivated by NF-kappaB in high-grade serous ovarian carcinoma. PG - 2089-2100 LID - 10.1038/cdd.2017.129 [doi] AB - 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-kappaB. 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. FAU - Wang, Yuqiong AU - Wang Y AD - Department of Cell Biology, Shandong University School of Medicine, Jinan 250012, China. AD - Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, China. FAU - Zhang, Xiyu AU - Zhang X AD - Department of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan 250012, China. FAU - Tang, Wei AU - Tang W AD - Department of Pathogenic Biology, Shandong University School of Medicine, Jinan 250012, China. FAU - Lin, Zhenghong AU - Lin Z AD - School of life Science, Chongqing University, Chongqing 401331, China. FAU - Xu, Limei AU - Xu L AD - Department of Cell Biology, Shandong University School of Medicine, Jinan 250012, China. FAU - Dong, Ruifen AU - Dong R AD - Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, China. FAU - Li, Yinuo AU - Li Y AD - Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, China. FAU - Li, Jieyin AU - Li J AD - Department of Cell Biology, Shandong University School of Medicine, Jinan 250012, China. FAU - Zhang, Zaixin AU - Zhang Z AD - Department of Cell Biology, Shandong University School of Medicine, Jinan 250012, China. FAU - Li, Xiangzhi AU - Li X AD - Department of Cell Biology, Shandong University School of Medicine, Jinan 250012, China. FAU - Zhao, Ling AU - Zhao L AD - Department of Cell Biology, Shandong University School of Medicine, Jinan 250012, China. FAU - Wei, Jian-Jun AU - Wei JJ AD - Department of Pathology, Northwestern University School of Medicine, Chicago, IL, USA. FAU - Shao, Changshun AU - Shao C AUID- ORCID: 0000-0003-2618-9342 AD - Department of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan 250012, China. FAU - Kong, Beihua AU - Kong B AD - Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, China. FAU - Liu, Zhaojian AU - Liu Z AD - Department of Cell Biology, Shandong University School of Medicine, Jinan 250012, China. LA - eng PT - Journal Article DEP - 20170811 PL - England TA - Cell Death Differ JT - Cell death and differentiation JID - 9437445 RN - 0 (MIRN130 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (NF-kappa B) RN - 0 (TSC1 protein, human) RN - 0 (Tsc1 protein, mouse) RN - 0 (Tuberous Sclerosis Complex 1 Protein) RN - 0 (Tumor Suppressor Proteins) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Cystadenocarcinoma, Serous/genetics/*metabolism/pathology MH - Female MH - HEK293 Cells MH - Heterografts MH - Humans MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - MicroRNAs/genetics/*metabolism MH - NF-kappa B/genetics/*metabolism MH - Neoplasm Grading MH - Ovarian Neoplasms/genetics/*metabolism/pathology MH - Retrospective Studies MH - Signal Transduction MH - TOR Serine-Threonine Kinases/genetics/*metabolism MH - Transfection MH - Tuberous Sclerosis Complex 1 Protein MH - Tumor Suppressor Proteins/genetics/*metabolism PMC - PMC5686346 COIS- The authors declare no conflict of interest. EDAT- 2017/08/12 06:00 MHDA- 2018/07/26 06:00 PMCR- 2018/12/01 CRDT- 2017/08/12 06:00 PHST- 2016/12/04 00:00 [received] PHST- 2017/06/23 00:00 [revised] PHST- 2017/07/05 00:00 [accepted] PHST- 2017/08/12 06:00 [pubmed] PHST- 2018/07/26 06:00 [medline] PHST- 2017/08/12 06:00 [entrez] PHST- 2018/12/01 00:00 [pmc-release] AID - cdd2017129 [pii] AID - 10.1038/cdd.2017.129 [doi] PST - ppublish SO - Cell Death Differ. 2017 Dec;24(12):2089-2100. doi: 10.1038/cdd.2017.129. Epub 2017 Aug 11.