SWELL1 Promotes Cell Proliferation And Migration In Hepatocellular Carcinoma In Vitro And In Vivo

Background and Objective Hepatocellular carcinoma(HCC)is a major health concern worldwide and the third most leading cause of cancer-associated mortality around the globe.Therefore,the elucidation of the predictive tumor biomarkers of HCC for early diagnosis and effective treatment is critical.SWELL1 is found to be an indispensable part of the volume-regulated anion channel(VRAC)recently.VRAC has been reported to participate in many cellular functions,such as cell migration and proliferation.However,the correlation between SWELL1 and cancer is yet ill-understood.Methods We investigated the expression levels of SWELL1 in 126 pairs of liver cancer samples and their adjacent nontumorous samples through the immunohistochemical staining.The method of q RT-PCR was used to confirm the result.The relationship between SWELL1 expression and clinicopathological characteristics including overall survival was analyzed.In order to assess whether SWELL1 is involved in cell proliferation and migration in vitro,the transwell migration assay,the wound healing assay,the CCK8 method and colony-forming assay were adopted.To study the role of SWELL1 in vivo,we developed nude mice models by subcutaneous and tail vein injections.In addition,we investigated the underlying molecular mechanism of SWELL1-mediated regulation of cell migration by Western blot.Result SWELL1 has been demonstrated to express highly in HCC tissues,and the high expression of SWELL1 is related to poor prognosis of HCC patients.In vitro,the knockdown of SWELL1 inhibited the cell migration and proliferation,whereas the overexpression of SWELL1 increased the cell migration and proliferation.Moreover,SWELL1 depletion by using sh RNA suppressed the growth and metastasis of HCC in vivo.Besides,further studies indicated that SWELL1 induced cell migration and proliferation by activating the JNK signaling pathway in HCC.Conclusion SWELL1 acts as a promoter in the proliferation and migration of HCC cells through the JNK pathway.SWELL1 may be a potential therapeutic target of HCC.