Long Noncoding RNA ADAMTS9-AS2 Inhibits the Proliferation, Migration, and Invasion in Bladder Tumor Cells

Zhan Zhang,1,* Jin-Peng Jia,2,* Yin-Jiang Zhang,3,* Gang Liu,4,5 Fan Zhou,6 Bi-Cheng Zhang7 1Department of Rehabilitation Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, People’s Republic of China; 2Department of Orthopaedics, General Hospital of Chinese People’s Liberation Army, Beijing 100853, People’s Republic of China; 3School of Pharmacy, Minzu University of China, Beijing 100081, People’s Republic of China; 4Department of Urology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi 435000, Hubei, People’s Republic of China; 5Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention, Hubei Polytechnic University, Huangshi 435000, Hubei, People’s Republic of China; 6Department of Urology, Wuhan Fourth Hospital, Pu’ai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430033, Hubei, People’s Republic of China; 7Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bi-Cheng Zhang Email bichengzhang@hotmail.comBackground: Bladder tumor is the fifth most prevalent tumor in men, yet its pathogenesis remains to be fully identified. Albeit a host of long noncoding RNAs (lncRNA) are emerging as new players involved in bladder tumor, the functions of many lncRNAs are still enigmatic. Reports on the deluge of studies on lncRNA ADAMTS9-AS2 have been convincingly associated with various tumors, but without mention of its roles in bladder tumor. Therefore, the roles of ADAMTS9-AS2 in bladder tumor cells were explored in our study.Materials and Methods: Quantitative real-time PCR assays and bioinformatic tools were applied in bladder tumor cells to identify the ADAMTS9-AS2 and ADAMTS9 expression. Western blot assays were performed to obtain the protein levels of bladder tumor related key molecules. CCK8, clonogenic assay, scratch wound healing, and transwell assays were separately applied to identify the functional roles of ADAMTS9-AS2 on proliferation, migration, and invasion in bladder tumor cells.Results: First, ADAMTS9-AS2 downregulation in bladder tumor cells was identified. Overexpression and knockdown experiments showed that ADAMTS9-AS2 expression was positively related to ADAMTS9, which is in accordance with the results from GEO database. Second, ADAMTS9-AS2 contributed to the inhibition of proliferation, migration, and invasion in bladder tumor cells. Third, ADAMTS9-AS2 was linked with PI3K/AKT/mTOR pathway related-molecules, several key autophagy, and apoptotic proteins.Conclusion: Conjointly, our findings suggested that ADAMTS9-AS2 might function as a tumor suppressor to restrain the proliferation, migration, and invasion in bladder tumor cells. The potential mechanism of ADAMTS9-AS2 related to PI3K/AKT/mTOR signal pathway was further identified. Of note, we found that ADAMTS9-AS2 has a significant effect on several key autophagy and apoptotic proteins. Therefore, these observations will provide supportive evidence to ADAMTS9-AS2 as a potential biomarker in patients with bladder tumor.Keywords: lncRNA ADAMTS9-AS2, proliferation, PI3K/AKT/mTOR, bladder tumor