Variant 2 of KIAA0101, antagonizing its oncogenic variant 1, might be a potential therapeutic strategy in hepatocellular carcinoma
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Lijuan Liu1,2, Youyi Liu1, Xiaobei Chen3, Miao Wang1, Yan Zhou1, Ping Zhou1, Wenxin Li2 and Fan Zhu1,4
1Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan 430071, P.R. China
2College of Life Sciences, Wuhan University, Wuhan 430072, P.R. China
3Department of Infectious Diseases, Ren-Min Hospital of Wuhan University, Wuhan 430060, P.R. China
4Hubei Province Key Laboratory of Allergy and Immunology, Wuhan 430071, P.R. China
Fan Zhu, email: [email protected], [email protected]
Keywords: hepatocellular carcinoma, alternative splicing, KIAA0101 transcript variant 2, isoform-selective competitor, therapeutic drug
Received: December 10, 2016 Accepted: March 06, 2017 Published: March 30, 2017
Hepatocellular carcinoma (HCC) is one of the most lethal malignant tumors worldwide and effective therapies, including molecular therapy, remain elusive. Our previous work demonstrates that oncogenic KIAA0101 transcript variant (tv) 1 promotes HCC development and might be a HCC therapeutic target. However, the function of another KIAA0101 variant, KIAA0101 tv2, remains unknown. In this study, we reported that KIAA0101 tv2 was highly expressed in adjacent non-tumorous liver tissues (NTs) compared to HCC tissues. In vivo and in vitro results showed that KIAA0101 tv2 decreased cell survival, colony formation, tumor xenografts, migration, and invasion, as well as induced cell cycle arrest and apoptosis. Interestingly, it could inhibit the function of KIAA0101 tv1 by partially down-regulating KIAA0101 tv1, acting similar to KIAA0101 tv1 short hairpin RNA (shRNA). Further studies illustrated that KIAA0101 tv2 could increase the activity of p53 by competing with KIAA0101 tv1 for P53 binding. In conclusion, KIAA0101 tv2 exerts anti-tumor activity in HCC and acts as an endogenous competitor of tumor-associated KIAA0101 tv1. KIAA0101 tv2 has a potential to work as a therapeutic drug targeting the KIAA0101 tv1 in HCC.
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