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Currently ranked as 5th most prevalent cancer type, liver cancer causes significant mortality across the globe. Additionally, the emergence of drug resistance and the alarming increase in the incidence of liver cancer has further worsened the situation. Therefore, development of effective chemotherapy, identification of molecular markers and therapeutic targets for proper treatment of liver cancer is the need of the hour. This study was undertaken to investigate the expression profile of hedgehog-interacting protein (HHIP) in liver cancer. Additionally, this study also investigated the effect of HHIP on the proliferation, migration and invasion of the human liver cancers. The expression analysis was done qRT-PCR. The cell viability was determined by MTT assay. Apoptosis was detected by annexin V/propidium iodide (PI) assay. Wound healing and transwell assays were used to monitor cell migration and invasion. Protein expression was determined by western blot analysis. The results showed a significant (6.8-fold) downregulation of HHIP in human liver cancer cells relative to the normal AML12 cells. Next, overexpression of HHIP resulted in significant (p<0.05) and time-dependent decrease in the growth of the HepG2 cells. The decrease in growth of the HepG2 cells was found to be mainly due to induction of apoptosis which was accompanied by increase in Bax and decrease in Bcl-2 expression. The wound healing assay showed that HHIP overexpression caused a remarkable decrease in the migration of the HepG2 cells. Furthermore, the transwell assay showed that the invasion of the HepG2 cells decreased by 65% upon HHIP overexpression. Taken together, HHIP may serve as potential molecular marker and therapeutic target for liver cancer management.


Xiaobin Wang, Wenjie Ma, Jun Yin, Meizhu Chen, Hong Jin. HHIP gene overexpression inhibits the growth, migration and invasion of human liver cancer cells. Journal of B.U.ON. : official journal of the Balkan Union of Oncology. 2020 Sep-Oct;25(5):2424-2429

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PMID: 33277865

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