Exosomal lncRNA ATB Derived from Ovarian Cancer Cells Promotes Angiogenesis via Regulating miR-204-3p/TGFβR2 Axis

Abstract

Donglan Yuan,1,* Ting Guo,2,* DanDan Zhu,1 Hongshan Ge,1 Yinling Zhao,1 Aihua Huang,1 Xiaosu Wang,1 Xiuhong Cao,3 CuiQin He,1 Hua Qian,1 Hong Yu4 1Department of Obstetrics and Gynecology, Taizhou People’s Hospital Affiliated to YangZhou University, Taizhou, Jiangsu, 225300, People’s Republic of China; 2Center for Molecular Medicine, Taizhou People’s Hospital Affiliated to YangZhou University, Taizhou, Jiangsu, 225300, People’s Republic of China; 3Department of Operation, Taizhou People’s Hospital Affiliated to YangZhou University, Taizhou, Jiangsu, 225300, People’s Republic of China; 4Department of Pathology, Taizhou People’s Hospital Affiliated to YangZhou University, Taizhou, Jiangsu, 225300, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hua QianDepartment of Obstetrics and Gynecology, Taizhou People’s Hospital Affiliated to YangZhou University, 399 Hailing Road, Hailing District, Taizhou, Jiangsu, 225300, People’s Republic of ChinaEmail [e-mail] YuDepartment of Pathology, Taizhou People’s Hospital Affiliated to YangZhou University, 399 Hailing Road, Hailing District, Taizhou, Jiangsu, 225300, People’s Republic of ChinaEmail [e-mail]: Ovarian cancer is a life-threatening disease with a high mortality rate in women. Our previous work presented that long non-coding RNA (lncRNA) activated by transforming growth factor beta (TGF-β) (lncRNA ATB) played a role of oncogene in ovarian cancer. However, whether exosomal lncRNA ATB from ovarian cancer cells could regulate the tumorigenesis of ovarian cancer remains unclear.Methods: RT-qPCR assay was performed to evaluate the level of lncRNA ATB in cancer cells (SKOV3 and A2780). In addition, ovarian cancer cells-secreted exosomes were collected with ultracentrifugation. CCK8 assay was performed to detect the viability of ovarian cells and HUVECs. Meanwhile, Western blot was performed to detect the expression of mechanism related protein and tube formation assay was used to observe the angiogenesis of HUVECs. Finally, xenograft mice model was used to verify the role of ovarian cancer cell-derived exosomes in vivo.Results: Ovarian cancer cells-derived exosomes promoted the viability, angiogenesis and migration of HUVECs; however, knockdown of lncRNA ATB in HUVECs reversed these phenomena. In addition, exosomal lncRNA ATB promoted the tumorigenesis of ovarian cancer via regulating miR-204-3p/TGFβR2 axis. Furthermore, ovarian cancer cells-secreted exosomal lncRNA ATB increased tumor growth in vivo.Conclusion: Exosomal lncRNA ATB derived from ovarian cancer cells could improve tumor microenvironment via regulating miR-204-3p/TGFβR2 axis. Thus, this study might provide new knowledge for the treatment of ovarian cancer.Keywords: ovarian cancer, exosome, lncRNA ATB, TGFβR2, tumor microenvironment