2017OncotargetOpen access

MicroRNA miR-147b promotes tumor growth via targeting UBE2N in hepatocellular carcinoma

En Zhang, Qin Liu, Yong Wang, Hui Wang, He Li, Xiuli Jin, Ning Li

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Abstract

// En Zhang 1, * , Qin Liu 2, * , Yong Wang 1 , Hui Wang 1 , Li He 1 , Xiuli Jin 1 and Ning Li 3 1 Department of Gastroenterology, The Second Affiliated Hospital of Shenyang Medical College, Shenyang 110035, China 2 Department of Gynecology and Obstetrics, Seventh People's Hospital of Shanghai University of TCM, Shanghai 200137, China 3 Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China * These authors have contributed equally to this work Correspondence to: En Zhang, email: 15840552727@139.com Ning Li, email: lining_hs@fudan.edu.cn Keywords: hepatocellular carcinoma; tumor growth; ubiquitin-conjugating enzyme E2N (UBE2N); miR-147b; microRNA Received: July 20, 2017 Accepted: November 30, 2017 Published: December 09, 2017 ABSTRACT As the subfamily of noncoding RNA, microRNAs (miRNAs) broadly regulate the development of cancers, while their dysregulation and function in human hepatocellular carcinoma (HCC) remains largely unclear. Here, we found the expression level of microRNA-147b (miR-147b) is increased aberrantly in HCC tumor tissues, and its expression positively correlates to the tumor severity. In both MTT and colony formation assay, knockdown of miR-147b dramatically inhibits in vitro proliferation of HCC cell lines. More interestingly, we also performed in vivo tumorigenesis assay and found that miR-147b can regulate in vivo tumorigenesis in nude mice xenograft models. The ubiquitin-conjugating enzyme E2N (UBE2N) was identified directly and functionally targeted by miR-147b. The mRNA level of UBE2N is increased in HCC tumors or cell lines. Restoring UBE2N expression level in tumor cells leads to inhibition of cell proliferation, which mimics the effect upon miR-147b knockdown in the same cells. These data elucidated the oncogenic role of miR-147b in HCC development and progression with therapeutic target potentials.

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// En Zhang 1, * , Qin Liu 2, * , Yong Wang 1 , Hui Wang 1 , Li He 1 , Xiuli Jin 1 and Ning Li 3 1 Department of Gastroenterology, The Second Affiliated Hospital of Shenyang Medical College, Shenyang 110035, China 2 Department of Gynecology and Obstetrics, Seventh People's Hospital of Shanghai University of TCM, Shanghai 200137, China 3 Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China * These authors have contributed equally to this work Correspondence to: En Zhang, email: 15840552727@139.com Ning Li, email: lining_hs@fudan.edu.cn Keywords: hepatocellular carcinoma; tumor growth; ubiquitin-conjugating enzyme E2N (UBE2N); miR-147b; microRNA Received: July 20, 2017 Accepted: November 30, 2017 Published: December 09, 2017 ABSTRACT As the subfamily of noncoding RNA, microRNAs (miRNAs) broadly regulate the development of cancers, while their dysregulation and function in human hepatocellular carcinoma (HCC) remains largely unclear. Here, we found the expression level of microRNA-147b (miR-147b) is increased aberrantly in HCC tumor tissues, and its expression positively correlates to the tumor severity. In both MTT and colony formation assay, knockdown of miR-147b dramatically inhibits in vitro proliferation of HCC cell lines. More interestingly, we also performed in vivo tumorigenesis assay and found that miR-147b can regulate in vivo tumorigenesis in nude mice xenograft models. The ubiquitin-conjugating enzyme E2N (UBE2N) was identified directly and functionally targeted by miR-147b. The mRNA level of UBE2N is increased in HCC tumors or cell lines. Restoring UBE2N expression level in tumor cells leads to inhibition of cell proliferation, which mimics the effect upon miR-147b knockdown in the same cells. These data elucidated the oncogenic role of miR-147b in HCC development and progression with therapeutic target potentials.

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Available abstract

// En Zhang 1, * , Qin Liu 2, * , Yong Wang 1 , Hui Wang 1 , Li He 1 , Xiuli Jin 1 and Ning Li 3 1 Department of Gastroenterology, The Second Affiliated Hospital of Shenyang Medical College, Shenyang 110035, China 2 Department of Gynecology and Obstetrics, Seventh People's Hospital of Shanghai University of TCM, Shanghai 200137, China 3 Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China * These authors have contributed equally to this work Correspondence to: En Zhang, email: 15840552727@139.com Ning Li, email: lining_hs@fudan.edu.cn Keywords: hepatocellular carcinoma; tumor growth; ubiquitin-conjugating enzyme E2N (UBE2N); miR-147b; microRNA Received: July 20, 2017 Accepted: November 30, 2017 Published: December 09, 2017 ABSTRACT As the subfamily of noncoding RNA, microRNAs (miRNAs) broadly regulate the development of cancers, while their dysregulation and function in human hepatocellular carcinoma (HCC) remains largely unclear. Here, we found the expression level of microRNA-147b (miR-147b) is increased aberrantly in HCC tumor tissues, and its expression positively correlates to the tumor severity. In both MTT and colony formation assay, knockdown of miR-147b dramatically inhibits in vitro proliferation of HCC cell lines. More interestingly, we also performed in vivo tumorigenesis assay and found that miR-147b can regulate in vivo tumorigenesis in nude mice xenograft models. The ubiquitin-conjugating enzyme E2N (UBE2N) was identified directly and functionally targeted by miR-147b. The mRNA level of UBE2N is increased in HCC tumors or cell lines. Restoring UBE2N expression level in tumor cells leads to inhibition of cell proliferation, which mimics the effect upon miR-147b knockdown in the same cells. These data elucidated the oncogenic role of miR-147b in HCC development and progression with therapeutic target potentials.

Key concepts: Gene knockdown, Carcinogenesis, microRNA, Hepatocellular carcinoma, Cancer research, Medicine, In vivo, Cell growth

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