J Cancer 2020; 11(22):6545-6555. doi:10.7150/jca.48333 This issue

Research Paper

miR-96 regulates liver tumor-initiating cells expansion by targeting TP53INP1 and predicts Sorafenib resistance

Yonggang Huang1#, Jin Zhang2#, HengYu Li3#, Huiping Peng4✉, Maolin Gu1✉, Hengjie Wang1✉

1. Department of Hepatic surgery, Kunshan Hospital of Traditional Chinese Medicine. Kunshan, Jiangsu Province, 215300, China.
2. Department of Hepatic Surgery, Third Affiliated Hospital of Second Military Medical University, Shanghai, 200438, China.
3. Department of General surgery, First Affiliated Hospital of Second Military Medical University, Shanghai, 200433, China.
4. Department of Gastroenterology, Kunshan Hospital of Traditional Chinese Medicine. Kunshan, Jiangsu Province, 215300, China.
#These authors contributed equally to this work.

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Citation:
Huang Y, Zhang J, Li H, Peng H, Gu M, Wang H. miR-96 regulates liver tumor-initiating cells expansion by targeting TP53INP1 and predicts Sorafenib resistance. J Cancer 2020; 11(22):6545-6555. doi:10.7150/jca.48333. Available from https://www.jcancer.org/v11p6545.htm

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Abstract

Liver tumor-initiating cells (T-ICs) contribute to tumorigenesis, progression, recurrence and drug resistance of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liver T-ICs remains unclear. In the present study, our finding shows that miR-96 is upregulated in liver T-ICs. Functional studies revealed that forced miR-96 promotes liver T-ICs self-renewal and tumorigenesis. Conversely, knockdown miR-96 inhibits liver T-ICs self-renewal and tumorigenesis. Mechanistically, miR-96 downregulates TP53INP1 via its mRNA 3'UTR in liver T-ICs. Furthermore, the miR-96 expression determines the responses of hepatoma cells to sorafenib treatment. Analysis of patient cohorts and patient-derived xenografts (PDXs) further demonstrate that the miR-96 may predict sorafenib benefits in HCC patients. Our findings revealed the crucial role of the miR-96 in liver T-ICs expansion and sorafenib response, rendering miR-96 as an optimal target for the prevention and intervention of HCC.

Keywords: hepatocellular carcinoma, tumor-initiating cells, miR-96, TP53INP1, sorafenib