LncRNA MBNL1-AS1 represses cell proliferation and enhances cell apoptosis via targeting miR-135a-5p/PHLPP2/FOXO1 axis in bladder cancer.

作者: Xiaosong Wei , Xiaoming Yang , Beibei Wang , Yang Yang , Zhiwei Fang

DOI: 10.1002/CAM4.2684

关键词:

摘要: LncRNAs have been shown to play essential roles in bladder cancer (BC) progress. Our microarrays of clinical samples firstly screened that lncRNA muscleblind-like 1 antisense RNA (MBNL1-AS1) was poorly expressed BC tissues. However, its biological function remains not well understood. Here we examined the correlations with MBNL1-AS1 patients. Then, 5673 and T24 cell lines were employed investigate role proliferation apoptosis cells vitro vivo. Furthermore, miR-135a-5p (miR-135a)/PHLPP2/FOXO1 axis focused explore regulatory mechanism BC. The results showed significantly downregulated tumor tissues, associated progression. In vitro, knockdown increased number viable bromodeoxyuridine-positive cells, accelerated cycle, dysregulated proliferative regulators (Ki67, p21, p27, Cyclin D1) cells. apoptotic cleavages caspase-3/9 reduced MBNL1-AS1-silenced Overexpression had opposite effects on apoptosis. Moreover miR-135a demonstrated interact MBNL1-AS1, inhibiting reversed shMBNL1-AS1 downstream effectors (PHLPP2 FOXO1) positively regulated by but negatively miR-135a. Similar also observed xenograft tumors. conclusion, this study suggests acts as a suppressor targeting miR-135a/PHLPP2/FOXO1 axis, providing novel insight for diagnosis treatment.

参考文章(29)
John Brognard, Emma Sierecki, Tianyan Gao, Alexandra C. Newton, PHLPP and a Second Isoform, PHLPP2, Differentially Attenuate the Amplitude of Akt Signaling by Regulating Distinct Akt Isoforms Molecular Cell. ,vol. 25, pp. 917- 931 ,(2007) , 10.1016/J.MOLCEL.2007.02.017
A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu, T. Murray, M. J. Thun, Cancer statistics, 2008. CA: A Cancer Journal for Clinicians. ,vol. 58, pp. 71- 96 ,(2008) , 10.3322/CA.2007.0010
Leonardo Salmena, Laura Poliseno, Yvonne Tay, Lev Kats, Pier Paolo Pandolfi, A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language? Cell. ,vol. 146, pp. 353- 358 ,(2011) , 10.1016/J.CELL.2011.07.014
Hui Yu, Qinghua Xu, Fang Liu, Xun Ye, Jialei Wang, Xia Meng, Identification and Validation of Long Noncoding RNA Biomarkers in Human Non–Small-Cell Lung Carcinomas Journal of Thoracic Oncology. ,vol. 10, pp. 645- 654 ,(2015) , 10.1097/JTO.0000000000000470
Tianyan Gao, Frank Furnari, Alexandra C. Newton, PHLPP: A Phosphatase that Directly Dephosphorylates Akt, Promotes Apoptosis, and Suppresses Tumor Growth Molecular Cell. ,vol. 18, pp. 13- 24 ,(2005) , 10.1016/J.MOLCEL.2005.03.008
Hans von der Maase, Lisa Sengelov, James T. Roberts, Sergio Ricci, Luigi Dogliotti, T. Oliver, Malcolm J. Moore, Annamaria Zimmermann, Michael Arning, Long-Term Survival Results of a Randomized Trial Comparing Gemcitabine Plus Cisplatin, With Methotrexate, Vinblastine, Doxorubicin, Plus Cisplatin in Patients With Bladder Cancer Journal of Clinical Oncology. ,vol. 23, pp. 4602- 4608 ,(2005) , 10.1200/JCO.2005.07.757
John P. Stein, Gary Lieskovsky, Richard Cote, Susan Groshen, An-Chen Feng, Stuart Boyd, Eila Skinner, Bernard Bochner, Duriayai Thangathurai, Maged Mikhail, Derek Raghavan, Donald G. Skinner, Radical Cystectomy in the Treatment of Invasive Bladder Cancer: Long-Term Results in 1,054 Patients Journal of Clinical Oncology. ,vol. 19, pp. 666- 675 ,(2001) , 10.1200/JCO.2001.19.3.666
Xiao Mao, Luo Zhang, Bin Huang, Shi Zhou, Jun Liao, Ling Chen, Shao Qiu, Jun Chen, Mir-135a enhances cellular proliferation through post-transcriptionally regulating PHLPP2 and FOXO1 in human bladder cancer Journal of Translational Medicine. ,vol. 13, pp. 86- 86 ,(2015) , 10.1186/S12967-015-0438-8
Xue-Yuan Dong, Ceshi Chen, Xiaodong Sun, Peng Guo, Robert L. Vessella, Ruo-Xiang Wang, Leland W.K. Chung, Wei Zhou, Jin-Tang Dong, FOXO1A Is a Candidate for the 13q14 Tumor Suppressor Gene Inhibiting Androgen Receptor Signaling in Prostate Cancer Cancer Research. ,vol. 66, pp. 6998- 7006 ,(2006) , 10.1158/0008-5472.CAN-06-0411