Heng Shi1, Jinbo Xie2, Keyi Wang2, Weiyi Li2, Lei Yin2, Guangchun Wang2, Zonglin Wu3, Jinliang Ni4, Weipu Mao5, Changcheng Guo6, Bo Peng7. 1. Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China; Department of Urology, Nantong Tongzhou People's Hospital, Nantong 226000, China. 2. Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China. 3. Department of Urology, Shidong Hospital of Shanghai, Shanghai 200438, China. 4. Shanghai Clinical College, Anhui Medical University, Shanghai 200072, China. 5. Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing 210009, China. 6. Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China. Electronic address: greatwall063030@126.com. 7. Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China. Electronic address: pengbo6908@163.com.
Abstract
BACKGROUND: The pathogenesis of bladder cancer (BLCa) is still unclear. Long non-coding RNAs (lncRNAs) participate in diverse biological processes across every branch of life, especially in cancer. Dysregulated lncRNAs in BLCa and their biological significance require further investigations. METHODS: Herein, a differential expression profile of lncRNAs in BLCa was conducted by microarray data. The expression level of lncRNA LINC01451 in 70 pairs of BLCa tissue samples and different BLCa cell lines were analyzed via real-time quantitative PCR. The CRISPR-CAS9 technique was employed to establish the LINC01451 stably transfected cell lines. Loss-of-function, as well as gain-of-function assays were carried out to evaluate the effects of LINC01451 on cell proliferation, migration, and invasion. Patient-derived xenograft (PDX) mouse models were adopted in the in vivo experiments. Western blot, biotinylated RNA probe pull-down assay, fluorescence in situ hybridization, and immunohistochemistry were utilized to assess the underlying molecular mechanisms of LINC01451 in BLCa. RESULTS: LINC01451 was identified a novel functional lncRNA, whose expression level in BLCa tissues was significantly higher compared with the normal tissues. Furthermore, it was found that LINC01451 directly docked LIN28A and LIN28B, and promoted the proliferation, invasion, and metastasis of BLCa. Mechanistically, LINC0145 was shown to depend on LIN28A and LIN28B, facilitated epithelial-mesenchymal transition (EMT) through activating the TGF-β/Smad signaling pathway, which subsequently aggravated BLCa progression. CONCLUSIONS: We demonstrates that LINC01451 drives EMT-induced BLCa progression by activating the LIN28/TGF-β/Smad signaling pathway. Promisingly, LINC01451 acts as a prognostic biomarker and a novel therapeutic target for BLCa.
BACKGROUND: The pathogenesis of bladder cancer (BLCa) is still unclear. Long non-coding RNAs (lncRNAs) participate in diverse biological processes across every branch of life, especially in cancer. Dysregulated lncRNAs in BLCa and their biological significance require further investigations. METHODS: Herein, a differential expression profile of lncRNAs in BLCa was conducted by microarray data. The expression level of lncRNA LINC01451 in 70 pairs of BLCa tissue samples and different BLCa cell lines were analyzed via real-time quantitative PCR. The CRISPR-CAS9 technique was employed to establish the LINC01451 stably transfected cell lines. Loss-of-function, as well as gain-of-function assays were carried out to evaluate the effects of LINC01451 on cell proliferation, migration, and invasion. Patient-derived xenograft (PDX) mouse models were adopted in the in vivo experiments. Western blot, biotinylated RNA probe pull-down assay, fluorescence in situ hybridization, and immunohistochemistry were utilized to assess the underlying molecular mechanisms of LINC01451 in BLCa. RESULTS: LINC01451 was identified a novel functional lncRNA, whose expression level in BLCa tissues was significantly higher compared with the normal tissues. Furthermore, it was found that LINC01451 directly docked LIN28A and LIN28B, and promoted the proliferation, invasion, and metastasis of BLCa. Mechanistically, LINC0145 was shown to depend on LIN28A and LIN28B, facilitated epithelial-mesenchymal transition (EMT) through activating the TGF-β/Smad signaling pathway, which subsequently aggravated BLCa progression. CONCLUSIONS: We demonstrates that LINC01451 drives EMT-induced BLCa progression by activating the LIN28/TGF-β/Smad signaling pathway. Promisingly, LINC01451 acts as a prognostic biomarker and a novel therapeutic target for BLCa.