Abstract
Long noncoding RNAs (lncRNAs) have been proved to play important roles in carcinogenesis and development of numerous cancers, but their biological functions in bladder cancer remain largely unknown. In this study, a novel lncRNA termed GAS6‐AS2 were primary identified, and its roles as well as mechanisms in regulating proliferation and metastasis of bladder cancer cells were investigated. Clinically, GAS6‐AS2 was significantly up‐regulated in bladder cancer tissues and positively correlated with tumour stages and poor prognosis. Moreover, expression of GAS6‐AS2 was also increased in bladder cancer cells compared with normal bladder cells. Further investigating the roles of GAS6‐AS2, we found GAS6‐AS2 regulated proliferation and proliferative activity of bladder cancer cells via inducing G1 phase arrest. What's more, we found that GAS6‐AS2 contributed to metastatic abilities of cells. In mechanism, GAS6‐AS2 could function as a competitive endogenous RNA (ceRNA) via direct sponging miR‐298, which further regulating the expression of CDK9. Finally, we also proved that GAS6‐AS2 knockdown suppressed tumour growth and metastasis in vivo. In conclusion, our study proved that GAS6‐AS2 could function as a ceRNA and promote the proliferation and metastasis of bladder cancer cells, which provided a novel prognostic marker for bladder cancer patients in clinic.
Highlights
Bladder cancer (BC) is one of the most common malignant cancers of the urinary system in China, and its incidence and mortality rates have increased in recent years.[1]
To further exploring the in‐depth mechanisms of GAS6‐AS2 involved in breast cancer progression, subcellular localization was firstly defined by nuclear mass separation experiment, and we found GAS6‐AS2 was mainly located in cytoplasm in both T24 and 5637 cell lines, which indicated that GAS6‐AS2 owned the potential ability of functioning as competitive endogenous RNA8 (Figure 5A)
It have been reported that about 60 000 Long noncoding RNAs (lncRNAs) have been identified, which account for about 60% of the cellular transcriptome,[20] and only no more than 4000 lncRNAs have been demonstrated aberrant expression and functional in cancers till now.[21]
Summary
Bladder cancer (BC) is one of the most common malignant cancers of the urinary system in China, and its incidence and mortality rates have increased in recent years.[1]. With NCYM to promote bladder cancer progression.[12] While the functions and mechanisms of lncRNAs are still remain largely unknown, it of great significance to explore novel lncRNAs and identify their functions, which might provide potential therapeutic targets for clinical treatments of bladder cancer patients. We primarily identified a novel lncRNA termed GAS6‐AS2, and our research proved that GAS6‐AS2 contributed to proliferation and metastasis of bladder cancer cells via the GAS6‐AS2/miR‐298/CDK9 axis. The research broadens our insights into the underlying mechanisms in proliferation and metastasis, and provided a new therapeutic target for bladder cancer patients in clinic
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