Abstract
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.
Highlights
Liver cancer is the second most lethal malignance worldwide, with more than half a million new cases diagnosed annually [1]
IHC showed KIAA0101 tv2-positive expression in 76.2% (32/42) of non-tumorous liver tissues (NTs) and in 31.0% (13/42) of Hepatocellular carcinoma (HCC) tissues (P
Because KIAA0101 tv2 was highly expressed in NTs compared to HCC, which was opposite to KIAA0101 tv1 expression, we explored whether the effects of KIAA0101 tv2
Summary
Liver cancer is the second most lethal malignance worldwide, with more than half a million new cases diagnosed annually [1]. Hepatocellular carcinoma (HCC) represents 90% of the total liver cancer cases, resulting in approximately 500,000 deaths per year [2]. Most patients with HCC are diagnosed with advanced disease due to its aggressive properties. Therapy options for most advanced HCC cases are limited. The multi-kinase inhibitor sorafenib is the only systemic therapy for advanced HCC, suggesting that molecular therapy could be effective for HCC. Sorafenib treatment only extends the median life expectancy of patients for 1 year [3, 4]. It is urgent to explore specific molecular targeted therapies for HCC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
