Department of Urology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
Department of Interventional Radiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
J Cell Physiol. 2020 Feb;235(2):1711-1722. doi: 10.1002/jcp.29090. Epub 2019 Jul 15.
Multifarious biological functions of long noncoding RNAs (lncRNAs) have been reported in various cancers including bladder cancer (BCa). This study aims to determine the biological role of a certain lncRNA in BCa. Consistent with the data of The Cancer Genome Atlas database, it was validated that lncRNA HLA complex group 22 (HCG22) was weakly expressed in BCa samples and lowly expressed HCG22 was closely correlated with low overall survival of the BCa patient. To verify the role of HCG22 in BCa progression, functional experiments were carried out in two representative BCa cells (J82 and T24) and the negative effects of HCG22 expression on the cell proliferation, migration, and epithelial-mesenchymal transition were identified. Mechanistically, polypyrimidine tract-binding protein 1 (PTBP1), which was highly expressed in BCa tissues and cell lines, was negatively regulated by HCG22 and the PTBP1-mediated Warburg effect was also obstructed by HCG22. Furthermore, HCG22 modulated the expression of PTBP1 through destabilizing human antigen R (HuR). And functional rescue assays confirmed that HCG22 functioned in bladder cancer through downregulating PTBP1. In conclusion, the present study revealed that HCG22 inhibited BCa progression via the HuR/PTBP1 axis, opening new prospects for potent therapeutic regimens for BCa patients.
长链非编码 RNA(lncRNA)在各种癌症中具有多种生物学功能,包括膀胱癌(BCa)。本研究旨在确定 lncRNA 在 BCa 中的生物学作用。与癌症基因组图谱数据库的数据一致,验证了 lncRNA HLA 复合物组 22(HCG22)在 BCa 样本中表达较弱,低表达的 HCG22 与 BCa 患者的总生存率低密切相关。为了验证 HCG22 在 BCa 进展中的作用,在两种代表性的 BCa 细胞(J82 和 T24)中进行了功能实验,确定了 HCG22 表达对细胞增殖、迁移和上皮-间充质转化的负作用。在机制上,多嘧啶 tract 结合蛋白 1(PTBP1)在 BCa 组织和细胞系中高表达,受 HCG22 负调控,HCG22 还阻断了 PTBP1 介导的瓦博格效应。此外,HCG22 通过不稳定人抗原 R(HuR)来调节 PTBP1 的表达。功能恢复实验证实,HCG22 通过下调 PTBP1 在膀胱癌中发挥作用。总之,本研究揭示了 HCG22 通过 HuR/PTBP1 轴抑制 BCa 进展,为 BCa 患者提供了新的治疗方案。