Upregulation of the long non-coding RNA, LIPCAR promotes proliferation, migration, and metastasis of hepatocellular carcinoma

Article type: Research Article

Authors: Bongolo, Christian Cedric^{a; 1} | Thokerunga, Erick^{a; 1} | Fidele, Nyimi Bushabu^b | Souraka, Tapara Dramani Maman^a | Kisembo, Peter^a | Rugera, Simon Peter^d | Worley, Paul F.^c | Tu, Jian-Cheng^{a; *}

Affiliations: [a] Program and Department of Clinical Laboratory Medicine and Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China | [b] Oral Maxillofacial Head and Neck Oncology Surgery, University of Kinshasa, Kinshasa, Democratic Republic of the Congo | [c] Department of Biomedical Sciences, Dental School and Program in Neuroscience, University of Maryland, Baltimore, MD, USA | [d] Department of Medical Laboratory Science, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda

Correspondence: [*] Corresponding author: Jian-Cheng Tu, Program and Department of Clinical Laboratory Medicine and Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China. Tel.: +86 13507119120; E-mail: [email protected].

Note: [1] Equal contribution authors.

Abstract: BACKGROUND: Hepatocellular carcinoma (HCC) early diagnosis remains a challenge to date. Alpha-feto protein, though less sensitive remains widely used for both diagnosis and prognosis. Recently however, a number of molecular biomarkers have been suggested as alternatives to Alpha feto protein, especially for early diagnosis. OBJECTIVE: To determine the role of the long non-coding RNA, LIPCAR in the pathogenesis and early diagnosis of hepatocellular carcinoma. METHODS: Quantitative real-time PCR, and Fluorescence in situ hybridization assays were conducted to determine LIPCAR expression in HCC vs normal blood samples, and HCC cell lines vs normal liver cell lines. Transfection was done to upregulate LIPCAR in one HCC cell line, and used to study cell proliferation, migration, apoptosis and epithelial-mesenchymal transformation. Animal experiment was finally done to determine its effect on metastasis. RESULTS: LIPCAR was significantly upregulated in HCC blood samples and HCC cell lines compared to their respective normal ones. Its overexpression promoted hepatocellular carcinoma cell proliferation, and migration, while inhibiting apoptosis. Its overexpression also promoted epithelial-mesenchymal transformation in hepatocellular carcinoma cells, and metastasis in vivo. CONCLUSION: The study demonstrated that the lncRNA, LIPCAR is significantly upregulated in hepatocellular carcinoma patients and that its upregulation promotes HCC proliferation, migration, and metastases.

Keywords: Hepatocellular carcinoma, long non-coding RNA, proliferation, invasion, metastasis

DOI: 10.3233/CBM-220033

Journal: Cancer Biomarkers, vol. 35, no. 3, pp. 245-256, 2022