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Open AccessArticle

Dysregulated FAM215A Stimulates LAMP2 Expression to Confer Drug-Resistant and Malignant in Human Liver Cancer

1
Department of Biochemistry, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
2
Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan
3
Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, and Chang Gung University, Taoyuan 333, Taiwan
4
Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
5
Neurosurgery, Fu Jen Catholic University Hospital and School of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan
6
Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan
7
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
*
Author to whom correspondence should be addressed.
Cells 2020, 9(4), 961; https://doi.org/10.3390/cells9040961
Received: 1 April 2020 / Revised: 13 April 2020 / Accepted: 13 April 2020 / Published: 14 April 2020
(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Hepatocellular Carcinoma)
Hepatocellular carcinoma (HCC) is one of the most common and aggressive human malignancies worldwide. Long non-coding (lnc) RNAs regulate complex cellular functions, such as cell growth, differentiation, metabolism, and metastasis. Although deregulation of lncRNA expression has been detected in HCC, many of the hepato-carcinogenesis-associated lncRNAs remain yet unidentified. Here, we aimed to investigate the involvement of a specific HCC-dysregulated lncRNA, FAM215A, and characterize its molecular regulation mechanism. We show for the first time that FAM215A is overexpressed in HCC, and its expression level correlates with tumor size, vascular invasion, and pathology stage. Overexpression of FAM215A accelerates cell proliferation and metastasis in HCC cells. According to Gene Expression Omnibus Dataset analysis, FAM215A is induced in doxorubicin (DOX)-resistant HCC cells. Overexpression of FAM215A increases DOX resistance in two HCC cell lines, and this is associated with enhanced expression of lysosome-associated membrane protein 2 (LAMP2). FAM215A interacts with LAMP2 to protect it from ubiquitination. Together, our results show that the lncRNA, FAM215A, is highly expressed in HCC, where it interacts with and stabilizes LAMP2 to increase tumor progression while decreasing doxorubicin sensitivity. View Full-Text
Keywords: HCC; Long non-coding RNA; FAM215A; Lysosome; LAMP2 HCC; Long non-coding RNA; FAM215A; Lysosome; LAMP2
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MDPI and ACS Style

Huang, P.-S.; Lin, Y.-H.; Chi, H.-C.; Tseng, Y.-H.; Chen, C.Y.; Lin, T.-K.; Yeh, C.-T.; Lin, K.-H. Dysregulated FAM215A Stimulates LAMP2 Expression to Confer Drug-Resistant and Malignant in Human Liver Cancer. Cells 2020, 9, 961.

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