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OBJECTIVE The aim of the study was to illustrate the function of circRNA ZFR in aggravating the development of hepatocellular carcinoma (HCC) by upregulating MAP2K1. PATIENTS AND METHODS CircRNA ZFR levels in 62 paired HCC and paracancerous species were detected. The influence of circRNA ZFR on clinical data of HCC patients was analyzed. After the overexpression or knockdown of circRNA ZFR, changes in viability and clonality of Bel-7402 and Hep3B cells were assessed, respectively. The involvement of circRNA ZFR/MAP2K1 axis in the development of HCC was explored through Luciferase assay and rescue experiments. RESULTS CircRNA ZFR was highly expressed in HCC species than the paracancerous ones. Higher level of circRNA ZFR predicted more advanced tumor grading of HCC. The knockdown of circRNA ZFR attenuated the proliferative ability of HCC cells, while the overexpression of circRNA ZFR obtained opposite results. MAP2K1 level was positively correlated to that of circRNA ZFR. Luciferase assay uncovered that circRNA ZFR can be targeted by MAP2K1 through specific binding sites. In addition, the overexpression of MAP2K1 could reverse the influence of silenced circRNA ZFR on proliferative ability of HCC cells. CONCLUSIONS CircRNA ZFR is upregulated in HCC and closely linked to tumor grading. It promotes proliferative ability in HCC by upregulating MAP2K1.