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LncRNA UCA1 Promotes Mitochondrial Function of Bladder Cancer via the MiR-195/ARL2 Signaling Pathway.
Cell Physiol Biochem. 2017; 43(6):2548-2561.CP

Abstract

BACKGROUND/AIMS

This study aims to identify whether Urothelial Cancer Associated 1 (UCA1) regulates mitochondrial metabolic reprogramming in bladder cancer, and to explore how UCA1 participates in mitochondrial metabolism by the UCA1/miR-195/ARL2 signaling pathway; these findings may be aid in the development of tumor diagnostic and therapeutic strategies.

METHODS

Bladder tissues were obtained from patients. Stable cell lines were constructed, with ectopic expression of UCA1 in UMUC2 cells and knockdown of UCA1 in 5637 cells. The expression levels of UCA1, miR-195, and ARL2 were detected by real-time PCR, western blotting, and immunohistochemistry Cell viability was detected by Cell Counting Kit-8 (CCK8) assay; mitochondrial DNA copy numbers were tested by realtime PCR; ATP level was evaluated by ATP assay kit; mitochondrial membrane potential was analyzed by 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolylcarbocyanine iodide (JC-1) fluorescent probe. miRNAs between UCA1 and ARL2 were predicted by TargetScan and RNAHybrid, and then determined by real-time PCR. Dual-luciferase activity assay and RNA immunoprecipitation (RIP) assay were used to verify the relationship between UCA1 and miR-195. The expression level of ARL2 was silenced by small interfering RNA(siRNA). For in vivo experiments, UCA1-silencing 5637 cells were subcutaneously injected into BALB/C nude mice to evaluate the effects of UCA1 on tumor progression by the regulation of miR-195 and ARL2.

RESULTS

We demonstrate here that UCA1 enhances mitochondrial function in bladder cancer cells. UCA1 contributes to ARL2-induced mitochondrial activity, which plays an important role in mitochondrial function. UCA1, as a competing endogenous RNA (ceRNA), regulates mitochondrial function through upregulating ARL2. In this way, it inhibited the miR-195 signaling pathway to enhance mitochondrial function in bladder cancer. Additionally, ARL2 is a direct target of miR-195 and can be repressed by either miR-195 overexpression or UCA1 inhibition. Knockdown of ARL2 was analogous to the inhibition of UCA1 and the upregulation of miR-195. Animal experiments further indicated that UCA1 promoted bladder tumor growth by regulating miR-195 /ARL2.

CONCLUSION

These data suggest that UCA1 enhanced mitochondrial function and cell viability through the UCA1/miR-195/ARL2 axis in vitro and in vivo. The elucidation of this signaling network provides a more adequate theoretical basis for understanding the molecular pathology of bladder cancer, and also UCA1 as a potential diagnosis and treatment target for bladder cancer.

Authors+Show Affiliations

Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Shaanxi, China.Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Shaanxi, China.Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Shaanxi, China.Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Shaanxi, China.Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Shaanxi, China.Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Shaanxi, China.Center for Translational Medicine, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Shaanxi, China.Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Shaanxi, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29130995

Citation

Li, Hui-Jin, et al. "LncRNA UCA1 Promotes Mitochondrial Function of Bladder Cancer Via the MiR-195/ARL2 Signaling Pathway." Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, vol. 43, no. 6, 2017, pp. 2548-2561.
Li HJ, Sun XM, Li ZK, et al. LncRNA UCA1 Promotes Mitochondrial Function of Bladder Cancer via the MiR-195/ARL2 Signaling Pathway. Cell Physiol Biochem. 2017;43(6):2548-2561.
Li, H. J., Sun, X. M., Li, Z. K., Yin, Q. W., Pang, H., Pan, J. J., Li, X., & Chen, W. (2017). LncRNA UCA1 Promotes Mitochondrial Function of Bladder Cancer via the MiR-195/ARL2 Signaling Pathway. Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology, 43(6), 2548-2561. https://doi.org/10.1159/000484507
Li HJ, et al. LncRNA UCA1 Promotes Mitochondrial Function of Bladder Cancer Via the MiR-195/ARL2 Signaling Pathway. Cell Physiol Biochem. 2017;43(6):2548-2561. PubMed PMID: 29130995.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - LncRNA UCA1 Promotes Mitochondrial Function of Bladder Cancer via the MiR-195/ARL2 Signaling Pathway. AU - Li,Hui-Jin, AU - Sun,Xiao-Min, AU - Li,Zheng-Kun, AU - Yin,Qian-Wen, AU - Pang,Huan, AU - Pan,Jing-Jing, AU - Li,Xu, AU - Chen,Wei, Y1 - 2017/11/01/ PY - 2017/06/27/received PY - 2017/09/29/accepted PY - 2017/11/14/pubmed PY - 2018/1/19/medline PY - 2017/11/14/entrez KW - ARL2 KW - Bladder cancer KW - LncRNA UCA1 KW - MiR-195 KW - Mitochondria SP - 2548 EP - 2561 JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JO - Cell. Physiol. Biochem. VL - 43 IS - 6 N2 - BACKGROUND/AIMS: This study aims to identify whether Urothelial Cancer Associated 1 (UCA1) regulates mitochondrial metabolic reprogramming in bladder cancer, and to explore how UCA1 participates in mitochondrial metabolism by the UCA1/miR-195/ARL2 signaling pathway; these findings may be aid in the development of tumor diagnostic and therapeutic strategies. METHODS: Bladder tissues were obtained from patients. Stable cell lines were constructed, with ectopic expression of UCA1 in UMUC2 cells and knockdown of UCA1 in 5637 cells. The expression levels of UCA1, miR-195, and ARL2 were detected by real-time PCR, western blotting, and immunohistochemistry Cell viability was detected by Cell Counting Kit-8 (CCK8) assay; mitochondrial DNA copy numbers were tested by realtime PCR; ATP level was evaluated by ATP assay kit; mitochondrial membrane potential was analyzed by 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolylcarbocyanine iodide (JC-1) fluorescent probe. miRNAs between UCA1 and ARL2 were predicted by TargetScan and RNAHybrid, and then determined by real-time PCR. Dual-luciferase activity assay and RNA immunoprecipitation (RIP) assay were used to verify the relationship between UCA1 and miR-195. The expression level of ARL2 was silenced by small interfering RNA(siRNA). For in vivo experiments, UCA1-silencing 5637 cells were subcutaneously injected into BALB/C nude mice to evaluate the effects of UCA1 on tumor progression by the regulation of miR-195 and ARL2. RESULTS: We demonstrate here that UCA1 enhances mitochondrial function in bladder cancer cells. UCA1 contributes to ARL2-induced mitochondrial activity, which plays an important role in mitochondrial function. UCA1, as a competing endogenous RNA (ceRNA), regulates mitochondrial function through upregulating ARL2. In this way, it inhibited the miR-195 signaling pathway to enhance mitochondrial function in bladder cancer. Additionally, ARL2 is a direct target of miR-195 and can be repressed by either miR-195 overexpression or UCA1 inhibition. Knockdown of ARL2 was analogous to the inhibition of UCA1 and the upregulation of miR-195. Animal experiments further indicated that UCA1 promoted bladder tumor growth by regulating miR-195 /ARL2. CONCLUSION: These data suggest that UCA1 enhanced mitochondrial function and cell viability through the UCA1/miR-195/ARL2 axis in vitro and in vivo. The elucidation of this signaling network provides a more adequate theoretical basis for understanding the molecular pathology of bladder cancer, and also UCA1 as a potential diagnosis and treatment target for bladder cancer. SN - 1421-9778 UR - https://www.unboundmedicine.com/medline/citation/29130995/LncRNA_UCA1_Promotes_Mitochondrial_Function_of_Bladder_Cancer_via_the_MiR_195/ARL2_Signaling_Pathway_ L2 - https://www.karger.com?DOI=10.1159/000484507 DB - PRIME DP - Unbound Medicine ER -