Abstract 4642: RNA interference reveals tumor promoting roles of integrin alpha 6 (ITGA6) in hepatocellular carcinoma

Abstract

Abstract Introduction: Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and the third leading cause of cancer related mortality. The incidence and mortality rates of HCC are two times higher in Latinos than in the general population in the US and are the highest in Latinos from the South Texas region. The genetic and epigenetic events associated with the increased incidence of HCC in this population are still unclear. Increasing evidence suggests that integrins are one of the most important receptors for cell metastasis including integrin α6β1 and α6β4. However, few studies have focused on the function of integrin alpha 6 (ITGA6) in the tumorigenesis and progression of HCC. We aim to investigate the expression and potential roles of ITGA6 in HCC. Materials and Methods: Paired HCC tissues and adjacent non-tumor tissues were collected for RNA sequencing. ITGA6 RNA and protein expression levels were evaluated by RNA sequencing, RT-qPCR, Western blot and immunohistochemistry. HCC cell lines (SNU398 and Huh7) were transiently transfected with two ITGA6siRNAs and stably transfected with an ITGA6 shRNA lentivector. These cell lines were used for assays testing the effects of ITGA6 knockdown on HCC cell proliferation, migration and anchorage independent growth. Results: Analysis of RNA sequencing data indicated that the expression of ITGA6 increased 4-fold in HCC tumor tissues compared to adjacent non-tumor tissues, which was validated by RT-qPCR. Western blotting also confirmed increased expression of ITGA6 in the tumor tissues. The knockdown of ITGA6 by siRNAs and shRNA was confirmed with Western blot and qRT-PCR. ITGA6 knockdown significantly decreased proliferation, migration and anchorage independent growth of HCC cell lines. Conclusions: ITGA6 is upregulated in HCC tumors in Latinos patients. ITGA6 may play a malignant-promoting role in HCC cells. Our studies provided new insights into the molecular mechanisms that drive HCC progression and potential therapeutic targets for treating patients with HCC including South Texas Latino patients. Citation Format: Guixi Zheng, Carla Zeballos, Hakim Bouamar, Matyas Cserhati, Francisco G Cigarroa, Lu-zhe Sun. RNA interference reveals tumor promoting roles of integrin alpha 6 (ITGA6) in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4642.