Hepatocellular carcinoma (HCC) is the most prominent form of presentation in liver cancer. It is also the fourth most common cause of cancer-associated deaths globally. The role of nucleus accumbens associated protein-1 (NACC-1) has been evaluated in several cancers. This protein is a transcriptional regulator that regulates a number of significant cellular processes. In the current study, we aimed to understand the role of NACC-1 in HCC. Primarily, we measured the expression of NACC-1 using quantitative real time polymerase chain reaction and western blot analysis. We knocked down the expression of NACC-1 in HCC cell lines Huh7 and HepG2 by transferring a commercially synthesized small interfering RNA and explored the impact of NACC-1 knockdown on cellular growth, migration, invasion, and chemoresistance to doxorubicin. Through bioinformatic analysis, we identified NACC-1 as a potential target of miR-760. Using a dual reporter luciferase assay, we confirmed the predicted target and assessed miR-760-mediated regulation of NACC-1 and rescue of tumorigenic phenotypes. We observed increased expression of NACC-1 in HCC. Furthermore, knockdown of NACC-1 resulted in reduced cell proliferation and invasion and increased susceptibility to doxorubicin-mediated chemosensitivity. Overexpression of miR-760 in HCC cell lines rescued NACC-1-mediated migration and invasion. We revealed that miR-760 regulated NACC-1 expression in HCC. Our data indicated that both miR-760 and NACC-1 could be used as prognostic markers, and miR-760 may have therapeutic benefits for HCC and other cancers.
Keywords: NACC-1; chemoresistance; hepatocellular carcinoma; miR-760.
© The Author(s) 2020. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please email: journals.permissions@oup.com.