RETRACTED: Long non-coding RNA LINC00152 promotes gallbladder cancer metastasis and epithelial–mesenchymal transition by regulating HIF-1α via miR-138

Open Biology - Tập 7 Số 1 - 2017
Qiang Cai1, Zhenqiang Wang2, Shouhua Wang1, Mingzhe Weng1, Di Zhou1, Chen Li2, Jiandong Wang1, Erzhen Chen3, Zhiwei Quan1
1Department of General Surgery, XinHua Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200092, People's Republic of China
2Shanghai Key Laboratory of Gastric Neoplasms, Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200025, People's Republic of China
3Department of Emergency, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200025, People's Republic of China

Tóm tắt

Long non-coding RNA LINC00152 had been reported as an oncogene in gastric and hepatocellular cancer. In this study, we show that LINC00152 is overexpressed in gallbladder cancer (GBC) tissue samples and cell lines. The high LINC00152 levels correlated negatively with the overall survival time in GBC patients. Functionally, LINC00152 dramatically promoted cell migration, invasion and epithelial–mesenchymal transition (EMT) progression in vitro. In vivo , LINC00152 overexpression significantly promoted tumour peritoneal spreading and metastasis. Mechanistic analyses indicated that LINC00152 functions as a molecular sponge for miR-138, which directly suppresses the expression of hypoxia inducible factor-1α (HIF-1α). We revealed that miR-138 is a suppressor of GBC cell metastasis and EMT progression, and a similar phenomenon was observed in HIF-1α knockdown NOZ cells. Through binding to miR-138, LINC00152 has an oncogenic effect on GBC. Overall, our study suggested that the LINC00152/miR-138/HIF-1α pathway potentiates the progression of GBC, and LINC00152 may be a novel therapeutic target.

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Tài liệu tham khảo

10.1634/theoncologist.2009-0302

10.1016/j.ijrobp.2008.10.052

Rakic M, Patrlj L, Kopljar M, Klicek R, Kolovrat M, Loncar B, Busic Z. 2014 Gallbladder cancer. Hepatobiliary Surg. Nutr. 3, 221–226. (doi:10.3978/j.issn.2304-3881.2014.09.03)

Wang SH, Wu XC, Zhang MD, Weng MZ, Zhou D, Quan ZW. 2016 Upregulation of H19 indicates a poor prognosis in gallbladder carcinoma and promotes epithelial-mesenchymal transition. Am. J. Cancer Res. 6, 15–26.

10.18632/oncotarget.8740

10.18632/oncotarget.4931

10.1016/j.canlet.2016.06.019

10.1038/onc.2011.383

10.1038/nm.3336

10.1016/j.cell.2009.01.002

10.1111/jcmm.12666

10.1159/000438590

10.1089/dna.2011.1544

10.1038/onc.2015.413

10.1038/cddis.2015.123

10.1002/hep.25870

10.1080/15384101.2015.1078034

10.1038/cddis.2014.541

10.1016/j.cell.2011.07.014

10.18632/oncotarget.6949

Ma F, Zhang M, Gong W, Weng M, Quan Z. 2015 MiR-138 suppresses cell proliferation by targeting Bag-1 in gallbladder carcinoma. PLoS ONE 10, e0126499. (doi:10.1371/journal.pone.0126499)

10.1073/pnas.0709971104

10.1002/ijc.28086

Song T, Zhang X, Wang C, Wu Y, Cai W, Gao J, Hong B. 2011 MiR-138 suppresses expression of hypoxia-inducible factor 1alpha (HIF-1alpha) in clear cell renal cell carcinoma 786-O cells. Asian Pac. J. Cancer Prev 12, 1307–1311.

10.1007/s10616-014-9763-7

10.1111/j.1478-3231.2012.02822.x

10.3892/ijo.2014.2753

Jin Z, Guan L, Song Y, Xiang GM, Chen SX, Gao B. 2016 MicroRNA-138 regulates chemoresistance in human non-small cell lung cancer via epithelial mesenchymal transition. Eur. Rev. Med. Pharmacol. Sci. 20, 1080–1086.

10.1042/BJ20111006

10.1371/journal.pone.0023752

Higgins DF et al. 2007 Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition. J. Clin. Invest. 117, 3810–3820. (doi:10.1172/jci30487)

10.1097/00029330-200605010-00002

10.1007/s10059-013-0096-8

10.1186/1471-2407-13-108

Zhang W et al. 2015 HIF-1α promotes epithelial-mesenchymal transition and metastasis through direct regulation of ZEB1 in colorectal cancer. PLoS ONE 10, e0129603. (doi:10.1371/journal.pone.0129603)

10.1074/jbc.M115.636944

10.1038/ncb1691

10.1593/neo.91326

10.1158/0008-5472.CAN-14-3721

10.1038/ncomms7779

10.1371/journal.pgen.1004467

10.1016/j.cell.2009.01.035

10.1002/hep.24563

Krishnamachary B et al. 2003 Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. Cancer Res. 63, 1138–1143.

10.3892/ijmm.2012.1064

10.4161/19336918.2014.972740