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MicroRNA-876-5p inhibits epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma by targeting BCL6 corepressor like 1.
Biomed Pharmacother. 2018 Jul; 103:645-652.BP

Abstract

Our previous study has reported that BCL6 corepressor like 1 (BCORL1) plays an oncogenic role in hepatocellular carcinoma (HCC) via promoting epithelial-mesenchymal transition (EMT) and tumor metastasis. However, the regulation of BCORL1 mediated by microRNAs (miRNAs) remains poorly known. The analysis of our clinical samples indicated that BCORL1 expression was markedly higher in HCC tissues than that in tumor-adjacent normal tissues. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets revealed that high BCORL1 expression associated with high tumor grade, advanced tumor stage and poor survival of HCC patients. miR-875-5p expression was down-regulated and negatively correlated with BCORL1 mRNA expression in HCC tissues. Furthermore, miR-876-5p inversely regulated BCORL1 abundance in HCC cells by directly targeting the 3'-untranslated region (3'-UTR) of BCORL1. Ectopic expression of miR-876-5p suppressed cell migration and invasion in both HCCLM3 and MHCC97H cells. In accordance, miR-876-5p knockdown promoted the metastatic behaviors of Hep3B cells. Mechanistically, miR-876-5p suppressed the EMT progression of HCC cells. HCC tissues with high miR-876-5p level showed a higher E-cadherin staining compared to cases with low miR-876-5p level. Moreover, the repression of cell metastasis mediated by miR-876-5p was rescued by BCORL1 restoration in HCCLM3 cells. Notably, low miR-876-5p expression associated with venous infiltration, high tumor grade and advanced tumor stage. HCC patients with low miR-876-5p expression had a significant poorer overall survival and disease-free survival. To conclude, miR-876-5p inhibits EMT progression, migration and invasion of HCC cells by targeting BCORL1. Therefore, miR-876-5p/BCORL1 axis may represent as a novel therapeutic target for HCC treatment.

Authors+Show Affiliations

Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang Province, 310014, China.Department of Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310000, China.Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, 510120, China.Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China.Department of Neurosurgery, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang Province, 310014, China.Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China.Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang Province, 310014, China. Electronic address: tongxiangmin@163.com.Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China. Electronic address: tks0912@foxmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29679906

Citation

Xu, Qiuran, et al. "MicroRNA-876-5p Inhibits Epithelial-mesenchymal Transition and Metastasis of Hepatocellular Carcinoma By Targeting BCL6 Corepressor Like 1." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 103, 2018, pp. 645-652.
Xu Q, Zhu Q, Zhou Z, et al. MicroRNA-876-5p inhibits epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma by targeting BCL6 corepressor like 1. Biomed Pharmacother. 2018;103:645-652.
Xu, Q., Zhu, Q., Zhou, Z., Wang, Y., Liu, X., Yin, G., Tong, X., & Tu, K. (2018). MicroRNA-876-5p inhibits epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma by targeting BCL6 corepressor like 1. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 103, 645-652. https://doi.org/10.1016/j.biopha.2018.04.037
Xu Q, et al. MicroRNA-876-5p Inhibits Epithelial-mesenchymal Transition and Metastasis of Hepatocellular Carcinoma By Targeting BCL6 Corepressor Like 1. Biomed Pharmacother. 2018;103:645-652. PubMed PMID: 29679906.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA-876-5p inhibits epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma by targeting BCL6 corepressor like 1. AU - Xu,Qiuran, AU - Zhu,Qiaojuan, AU - Zhou,Zhenyu, AU - Wang,Yufeng, AU - Liu,Xin, AU - Yin,Guozhi, AU - Tong,Xiangmin, AU - Tu,Kangsheng, Y1 - 2018/04/24/ PY - 2018/03/06/received PY - 2018/04/04/revised PY - 2018/04/05/accepted PY - 2018/4/22/pubmed PY - 2018/10/10/medline PY - 2018/4/22/entrez KW - BCORL1 KW - EMT KW - Hepatocellular carcionoma KW - Tumor metastasis KW - miR-876-5p SP - 645 EP - 652 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed. Pharmacother. VL - 103 N2 - Our previous study has reported that BCL6 corepressor like 1 (BCORL1) plays an oncogenic role in hepatocellular carcinoma (HCC) via promoting epithelial-mesenchymal transition (EMT) and tumor metastasis. However, the regulation of BCORL1 mediated by microRNAs (miRNAs) remains poorly known. The analysis of our clinical samples indicated that BCORL1 expression was markedly higher in HCC tissues than that in tumor-adjacent normal tissues. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets revealed that high BCORL1 expression associated with high tumor grade, advanced tumor stage and poor survival of HCC patients. miR-875-5p expression was down-regulated and negatively correlated with BCORL1 mRNA expression in HCC tissues. Furthermore, miR-876-5p inversely regulated BCORL1 abundance in HCC cells by directly targeting the 3'-untranslated region (3'-UTR) of BCORL1. Ectopic expression of miR-876-5p suppressed cell migration and invasion in both HCCLM3 and MHCC97H cells. In accordance, miR-876-5p knockdown promoted the metastatic behaviors of Hep3B cells. Mechanistically, miR-876-5p suppressed the EMT progression of HCC cells. HCC tissues with high miR-876-5p level showed a higher E-cadherin staining compared to cases with low miR-876-5p level. Moreover, the repression of cell metastasis mediated by miR-876-5p was rescued by BCORL1 restoration in HCCLM3 cells. Notably, low miR-876-5p expression associated with venous infiltration, high tumor grade and advanced tumor stage. HCC patients with low miR-876-5p expression had a significant poorer overall survival and disease-free survival. To conclude, miR-876-5p inhibits EMT progression, migration and invasion of HCC cells by targeting BCORL1. Therefore, miR-876-5p/BCORL1 axis may represent as a novel therapeutic target for HCC treatment. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/29679906/MicroRNA_876_5p_inhibits_epithelial_mesenchymal_transition_and_metastasis_of_hepatocellular_carcinoma_by_targeting_BCL6_corepressor_like_1_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(18)31497-5 DB - PRIME DP - Unbound Medicine ER -