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Your search keyword '"Jiang, Yangkai"' showing total 11 results
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11 results on '"Jiang, Yangkai"'

8. Regulation of CD8+T cells infiltration and immunotherapy by circMGA/HNRNPL complex in bladder cancer

Author

Sun, Jiayin, Zhang, Hui, Wei, Wenjie, Xiao, Xingyuan, Huang, Chao, Wang, Liang, Zhong, He, Jiang, Yangkai, Zheng, Fuxin, Yang, Hongmei, Jiang, Guosong, and Zhang, Xiaoping

Abstract

The limited success of immunotherapies targeting immune checkpoint inhibitors is largely ascribed to the lack of infiltrating CD8+T lymphocytes. Circular RNAs (circRNAs) are a novel type of prevalent noncoding RNA that have been implicated in tumorigenesis and progression, while their roles in modulating CD8+T cells infiltration and immunotherapy in bladder cancer have not yet been investigated. Herein, we uncover circMGA as a tumor-suppressing circRNA triggering CD8+T cells chemoattraction and boosting the immunotherapy efficacy. Mechanistically, circMGA functions to stabilize CCL5 mRNA by interacting with HNRNPL. In turn, HNRNPL increases the stability of circMGA, forming a feedback loop that enhances the function of circMGA/HNRNPL complex. Intriguingly, therapeutic synergy between circMGA and anti-PD-1 could significantly suppress xenograft bladder cancer growth. Taken together, the results demonstrate that circMGA/HNRNPL complex may be targetable for cancer immunotherapy and the study advances our understanding of the physiological roles of circRNAs in antitumor immunity.

Published
2023
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11. Circ0008399 Interaction with WTAP Promotes Assembly and Activity of the m 6 A Methyltransferase Complex and Promotes Cisplatin Resistance in Bladder Cancer.

Author

Wei W, Sun J, Zhang H, Xiao X, Huang C, Wang L, Zhong H, Jiang Y, Zhang X, and Jiang G

Subjects
Animals, Antineoplastic Agents pharmacology, Apoptosis, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Cell Cycle Proteins genetics, Cell Proliferation, Female, Humans, Male, Methyltransferases genetics, Mice, Mice, Inbred BALB C, Mice, Nude, Middle Aged, Prognosis, RNA Splicing Factors genetics, Survival Rate, Tumor Cells, Cultured, Tumor Necrosis Factor alpha-Induced Protein 3 genetics, Tumor Necrosis Factor alpha-Induced Protein 3 metabolism, Urinary Bladder Neoplasms genetics, Urinary Bladder Neoplasms metabolism, Urinary Bladder Neoplasms pathology, Xenograft Model Antitumor Assays, Cell Cycle Proteins metabolism, Cisplatin pharmacology, Drug Resistance, Neoplasm, Gene Expression Regulation, Neoplastic drug effects, Methyltransferases metabolism, RNA Splicing Factors metabolism, RNA, Circular genetics, Urinary Bladder Neoplasms drug therapy
Abstract

Cisplatin (CDDP)-based chemotherapy is the first-line treatment for muscle-invasive and metastatic bladder cancer, yet most patients rapidly develop resistance. N6-methyladenosine (m 6 A) methylation is a pervasive RNA modification, and its specific role and potential mechanism in the regulation of CDDP chemosensitivity in bladder cancer remain unclear. Furthermore, studies have not yet fully elucidated whether circular RNA (circRNA) can directly regulate m 6 A modification of mRNA. Here we report upregulation of a novel circRNA, hsa_circ_0008399 ( circ0008399 ), by eukaryotic translation initiation factor 4A3 (EIF4A3) in bladder cancer tissues and cell lines. Functionally, circ0008399 inhibited apoptosis of bladder cancer cells. Mechanistically, circ0008399 bound Wilms' tumor 1-associating protein (WTAP) to promote formation of the WTAP/METTL3/METTL14 m 6 A methyltransferase complex. Circ0008399 increased expression of TNF alpha-induced protein 3 (TNFAIP3) by increasing its mRNA stability in an m 6 A-dependent manner. In patients with bladder cancer, high expression of circ0008399 and WTAP was associated with poor outcomes. Importantly, activation of the circ0008399 /WTAP/TNFAIP3 pathway decreased bladder cancer chemosensitivity to CDDP, and targeting the circ0008399 /WTAP/TNFAIP3 axis enhanced the CDDP efficacy. Collectively, these findings give novel insights into circRNA-mediated regulation of m 6 A modifications and provide potential therapeutic targets for bladder cancer. SIGNIFICANCE: A newly characterized circRNA circ0008399 binds WTAP to modulate expression of target RNA through m 6 A modification and reduce cisplatin sensitivity in bladder cancer, implicating the potential therapeutic value of targeting this axis., (©2021 American Association for Cancer Research.)

Published
2021
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