Long noncoding RNA LINC00662 promotes M2 macrophage polarization and hepatocellular carcinoma progression via activating Wnt/β-catenin signaling

被引：182

作者：

Tian, Xiaohui ^{[1
]}

Wu, Yuanyuan ^{[2
]}

Yang, Yating ^{[2
]}

Wang, Jiaxin ^{[2
]}

Niu, Menglan ^{[2
]}

Gao, Shanjun ^{[3
]}

Qin, Tao ^{[4
]}

Bao, Dengke ^{[1
,2
,4
]}

机构：

[1] Henan Univ Peoples Hosp, Henan Prov Peoples Hosp, Dept Clin Lab, Zhengzhou, Henan, Peoples R China

[2] Henan Univ, Sch Pharm, Lab Canc Biomarkers & Liquid Biopsy, Kaifeng, Peoples R China

[3] Henan Univ Peoples Hosp, Henan Prov Peoples Hosp, Microbiome Lab, Zhengzhou, Henan, Peoples R China

[4] Henan Univ Peoples Hosp, Henan Prov Peoples Hosp, Dept Hepatobiliary Pancreat Surg, Zhengzhou, Henan, Peoples R China

来源：

MOLECULAR ONCOLOGY | 2020年 / 14卷 / 02期

基金：

中国国家自然科学基金;

关键词：

ceRNA; hepatocellular carcinoma; LINC00662; long noncoding RNA; macrophage polarization; Wnt; beta-catenin signaling; PROSTATE-CANCER; METASTASIS; PROLIFERATION; CONTRIBUTES; DIFFERENTIATION; INHIBITION; LANDSCAPE; NETWORK; GROWTH; LNCRNA;

D O I：

10.1002/1878-0261.12606

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Tumor-associated macrophages have important roles in hepatocellular carcinoma (HCC) initiation and progression. Long noncoding RNAs (lncRNAs) have also been reported to be involved in HCC. In this study, we explored how lncRNA LINC00662 may influence HCC progression through both tumor cell-dependent and macrophage-dependent mechanisms. LINC00662 was found to be upregulated in HCC, and high LINC00662 levels correlated with poor survival of HCC patients. LINC00662 upregulated WNT3A expression and secretion via competitively binding miR-15a, miR-16, and miR-107. Through inducing WNT3A secretion, LINC00662 activated Wnt/beta-catenin signaling in HCC cells in an autocrine manner and further promoted HCC cell proliferation, cell cycle, and tumor cell invasion, while repressing HCC cell apoptosis. In addition, acting through WNT3A secretion, LINC00662 activated Wnt/beta-catenin signaling in macrophages in a paracrine manner and further promoted M2 macrophage polarization. Via activating Wnt/beta-catenin signaling and M2 macrophages polarization, LINC00662 significantly promoted HCC tumor growth and metastasis in vivo. Hence, targeting LINC00662 may provide novel therapeutic strategy against HCC.

引用

页码：462 / 483

页数：22

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