J Cancer 2021; 12(11):3098-3113. doi:10.7150/jca.56340

Research Paper

Highly deregulated lncRNA LOC is associated with overall worse prognosis in Hepatocellular Carcinoma patients

Lee Jin Lim1, Lay Hiang Ling1, Yu Pei Neo1,3, Alexander Y.F. Chung2, Brian K.P. Goh2, Pierce K.H. Chow2,3,4, Chung Yip Chan2, Peng Chung Cheow2, Ser Yee Lee2, Tony K.H. Lim5, Samuel S. Chong7, London L. P. J. Ooi2,3,4, Caroline G. Lee1,3,6,8✉

1. Dept of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
2. Dept of Hepato-pancreato-biliary & Transplant Surgery, Singapore General Hospital, Singapore.
3. Duke-NUS Medical School, Singapore.
4. Dept of Surgical Oncology, National Cancer Centre Singapore, Singapore.
5. Dept of Pathology, Singapore General Hospital, Singapore.
6. Div of Cellular & Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, Singapore.
7. Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
8. NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.

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Citation:
Lim LJ, Ling LH, Neo YP, Chung AYF, Goh BKP, Chow PKH, Chan CY, Cheow PC, Lee SY, Lim TKH, Chong SS, Ooi LLPJ, Lee CG. Highly deregulated lncRNA LOC is associated with overall worse prognosis in Hepatocellular Carcinoma patients. J Cancer 2021; 12(11):3098-3113. doi:10.7150/jca.56340. Available from https://www.jcancer.org/v12p3098.htm

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Abstract

Although numerous long non-coding RNAs (lncRNAs) were reported to be deregulated in Hepatocellular Carcinoma (HCC), experimentally characterized, and/or associated with patient's clinical characteristics, there is, thus far, minimal concerted research strategy to identify deregulated lncRNAs that modulate prognosis of HCC patients. Here, we present a novel strategy where we identify lncRNAs, which are not only de-regulated in HCC patients, but are also associated with pertinent clinical characteristics, potentially contributing to the prognosis of HCC patients. LOC101926913 (LOC) was further characterized because it is the most highly differentially expressed amongst those that are associated with the most number of clinical features (tumor-stage, vascular and tumor invasion and poorer overall survival). Experimental gain- and loss-of-function manipulation of LOC in liver cell-lines highlight LOC as a potential onco-lncRNA promoting cell proliferation, anchorage independent growth and invasion. LOC expression in cells up-regulated genes involved in GTPase-activities and downregulated genes associated with cellular detoxification, oxygen- and drug-transport. Hence, LOC may represent a novel therapeutic target, modulating prognosis of HCC patients through up-regulating GTPase-activities and down-regulating detoxification, oxygen- and drug-transport. This strategy may thus be useful for the identification of clinically relevant lncRNAs as potential biomarkers/targets that modulate prognosis in other cancers as well.

Keywords: Hepatocellular Carcinoma, Long non-coding RNA, Prognosis, Hepatocarcinogenesis, LOC101926913