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MiR-338-3p inhibits hepatocarcinoma cells and sensitizes these cells to sorafenib by targeting hypoxia-induced factor 1α.
PLoS One. 2014; 9(12):e115565.Plos

Abstract

Hypoxia is a common feature of solid tumors and an important contributor to anti-tumor drug resistance. Hypoxia inducible factor-1 (HIF-1) is one of the key mediators of the hypoxia signaling pathway, and was recently proven to be required for sorafenib resistance in hepatocarcinoma (HCC). MicroRNAs have emerged as important posttranslational regulators in HCC. It was reported that miR-338-3p levels are associated with clinical aggressiveness of HCC. However, the roles of miR-338-3p in HCC disease and resistance to its therapeutic drugs are unknown. In this study, we found that miR-338-3p was frequently down-regulated in 14 HCC clinical samples and five cell lines. Overexpression of miR-338-3p inhibited HIF-1α 3'-UTR luciferase activity and HIF-1α protein levels in HepG2, SMMC-7721, and Huh7 cells. miR-338-3p significantly reduced cell viability and induced cell apoptosis of HCC cells. Additionally, HIF-1α overexpression rescued and HIF-1α knock-down abrogated the anti-HCC activity of miR-338-3p. Furthermore, miR-338-3p sensitized HCC cells to sorafenib in vitro and in a HCC subcutaneous nude mice tumor model by inhibiting HIF-1α. Collectively, miR-338-3p inhibits HCC tumor growth and sensitizes HCC cells to sorafenib by down-regulating HIF-1α. Our data indicate that miR-338-3p could be a potential candidate for HCC therapeutics.

Authors+Show Affiliations

Department of Hepatopancreatobiliary Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, P.R. China.Department of Hepatopancreatobiliary Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, P.R. China.Department of Internal Medicine, The Heilongjiang Provincial Hospital, Harbin, Heilongjiang, P.R. China.Department of Hepatopancreatobiliary Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, P.R. China.Department of Hepatopancreatobiliary Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, P.R. China.Department of Hepatopancreatobiliary Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, P.R. China.Department of Operations, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, P.R. China.Department of Hepatopancreatobiliary Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, P.R. China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25531114

Citation

Xu, Haitao, et al. "MiR-338-3p Inhibits Hepatocarcinoma Cells and Sensitizes These Cells to Sorafenib By Targeting Hypoxia-induced Factor 1α." PloS One, vol. 9, no. 12, 2014, pp. e115565.
Xu H, Zhao L, Fang Q, et al. MiR-338-3p inhibits hepatocarcinoma cells and sensitizes these cells to sorafenib by targeting hypoxia-induced factor 1α. PLoS One. 2014;9(12):e115565.
Xu, H., Zhao, L., Fang, Q., Sun, J., Zhang, S., Zhan, C., Liu, S., & Zhang, Y. (2014). MiR-338-3p inhibits hepatocarcinoma cells and sensitizes these cells to sorafenib by targeting hypoxia-induced factor 1α. PloS One, 9(12), e115565. https://doi.org/10.1371/journal.pone.0115565
Xu H, et al. MiR-338-3p Inhibits Hepatocarcinoma Cells and Sensitizes These Cells to Sorafenib By Targeting Hypoxia-induced Factor 1α. PLoS One. 2014;9(12):e115565. PubMed PMID: 25531114.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MiR-338-3p inhibits hepatocarcinoma cells and sensitizes these cells to sorafenib by targeting hypoxia-induced factor 1α. AU - Xu,Haitao, AU - Zhao,Liang, AU - Fang,Qiuju, AU - Sun,Jianmin, AU - Zhang,Songyan, AU - Zhan,Chao, AU - Liu,Shujie, AU - Zhang,Yubao, Y1 - 2014/12/22/ PY - 2014/07/02/received PY - 2014/11/25/accepted PY - 2014/12/23/entrez PY - 2014/12/23/pubmed PY - 2015/12/17/medline SP - e115565 EP - e115565 JF - PloS one JO - PLoS One VL - 9 IS - 12 N2 - Hypoxia is a common feature of solid tumors and an important contributor to anti-tumor drug resistance. Hypoxia inducible factor-1 (HIF-1) is one of the key mediators of the hypoxia signaling pathway, and was recently proven to be required for sorafenib resistance in hepatocarcinoma (HCC). MicroRNAs have emerged as important posttranslational regulators in HCC. It was reported that miR-338-3p levels are associated with clinical aggressiveness of HCC. However, the roles of miR-338-3p in HCC disease and resistance to its therapeutic drugs are unknown. In this study, we found that miR-338-3p was frequently down-regulated in 14 HCC clinical samples and five cell lines. Overexpression of miR-338-3p inhibited HIF-1α 3'-UTR luciferase activity and HIF-1α protein levels in HepG2, SMMC-7721, and Huh7 cells. miR-338-3p significantly reduced cell viability and induced cell apoptosis of HCC cells. Additionally, HIF-1α overexpression rescued and HIF-1α knock-down abrogated the anti-HCC activity of miR-338-3p. Furthermore, miR-338-3p sensitized HCC cells to sorafenib in vitro and in a HCC subcutaneous nude mice tumor model by inhibiting HIF-1α. Collectively, miR-338-3p inhibits HCC tumor growth and sensitizes HCC cells to sorafenib by down-regulating HIF-1α. Our data indicate that miR-338-3p could be a potential candidate for HCC therapeutics. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/25531114/MiR_338_3p_inhibits_hepatocarcinoma_cells_and_sensitizes_these_cells_to_sorafenib_by_targeting_hypoxia_induced_factor_1α_ L2 - https://dx.plos.org/10.1371/journal.pone.0115565 DB - PRIME DP - Unbound Medicine ER -