Abstract
Long intergenic noncoding RNAs (lincRNAs) play important roles in regulating various biological processes in cancer, including proliferation and apoptosis. However, the roles of lincRNAs in bladder cancer remain elusive. In this study, we identified a novel lincRNA, which we termed AATBC. We found that AATBC was overexpressed in bladder cancer patient tissues and positively correlated with tumor grade and pT stage. We also found that inhibition of AATBC resulted in cell proliferation arrest through G1 cell cycle mediated by cyclin D1, CDK4, p18 and phosphorylated Rb. In addition, inhibition of AATBC induced cell apoptosis through the intrinsic apoptosis signaling pathway, as evidenced by the activation of caspase-9 and caspase-3. The investigation for the signaling pathway revealed that the apoptosis following AATBC knockdown was mediated by activation of phosphorylated JNK and suppression of NRF2. Furthermore, JNK inhibitor SP600125 could attenuate the apoptotic effect achieved by AATBC knockdown, confirming the involvement of JNK signaling in the induced apoptosis. Moreover, mouse xenograft model revealed that knockdown of AATBC led to suppress tumorigenesis in vivo. Taken together, our study indicated that AATBC might play a critical role in pro-proliferation and anti-apoptosis in bladder cancer by regulating cell cycle, intrinsic apoptosis signaling, JNK signaling and NRF2. AATBC could be a potential therapeutic target and molecular biomarker for bladder cancer.
Highlights
Bladder cancer is a common malignant tumor of genitourinary system[1]
Our study indicated that AATBC might play a critical role in pro-proliferation and anti-apoptosis in bladder cancer by regulating cell cycle, intrinsic apoptosis signaling, JNK signaling and NF-E2-related factor 2 (NRF2)
To investigate the potential biological functions of lincRNAs in bladder cancer, we firstly examined the expression pattern of lincRNAs and mRNAs in matched sets of muscle invasive bladder cancer tissues and adjacent non tumor tissues obtained from 5 patients
Summary
Bladder cancer is a common malignant tumor of genitourinary system[1]. 70% of the cases are non-muscle invasive bladder cancer (NMIBC) that can be resected. Some of these cases will progress to muscle invasive bladder cancer (MIBC) or metastasis to distant organs and endanger the lives of patients. It is an urgent need to study the carcinogenesis and progression of bladder cancer. Studies showed that abnormal expression of lincRNA is in a disease-, tissue- or www.impactjournals.com/oncotarget developmental stage-specific manner[9, 10]. Some lincRNAs are involved in pathological processes of cancer, such as proliferation, apoptosis, invasion and metastasis, acting as tumor suppressor genes or oncogenes in various types of cancer[11, 12]. The objective of our study is to elucidate the lincRNAs expression patterns between bladder cancer and normal bladder tissues and try to find a specific lincRNA that may be a potential therapeutic target or biomarker for bladder cancer
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