Downregulation of microRNA-326 enhances ZNF322A expression, transcriptional activity and tumorigenic effects in lung cancer

doi:10.1002/biof.2004

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標題:	Downregulation of microRNA-326 enhances ZNF322A expression, transcriptional activity and tumorigenic effects in lung cancer
作者:	Huang, Shih-Hsuan Hsieh, Hung-Chia Shieh, Jiunn-Min Su, Wou-Chou Wang, Yi-Ching
貢獻者:	Natl Cheng Kung Univ, Coll Med, Dept Pharmacol Natl Cheng Kung Univ, Inst Basic Med Sci, Coll Med Chi Mei Med Ctr, Dept Internal Med, Div Chest Med Chia Nan Univ Pharm & Sci, Ctr Gen Educ Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Internal Med,Div Oncol Natl Cheng Kung Univ, Dept Pharmacol Natl Cheng Kung Univ, Inst Basic Med Sci
關鍵字:	lung cancer miR-326 prognosis transcription ZNF322A
日期:	2024
上傳時間:	2024-12-25 11:05:11 (UTC+8)
出版者:	WILEY
摘要:	Zinc finger protein ZNF322A is an oncogenic transcription factor. Overexpression of ZNF322A activates pro-metastasis, cancer stemness, and neo-angiogenesis-related genes to enhance lung cancer progression. However, the upstream regulator of ZNF322A is not well defined. Dysregulation of microRNAs (miRNAs) can mediate cancer cell growth, migration, and invasion to promote tumorigenesis. Here, we uncover the mechanism of miRNA-mediated transcriptional regulation in ZNF322A-driven oncogenic events. ZNF322A harbors several putative miRNA-binding sites in the 3'-untranslated region (UTR). We validated that miR-326 downregulated ZNF322A-3'-UTR luciferase activity and mRNA expression. Furthermore, miR-326 suppressed the expression of ZNF322A-driven cancer-associated genes such as cyclin D1 and alpha-adducin. Reconstitution experiments by ectopic overexpression of ZNF322A abolished miR-326-suppressed cancer cell proliferation and cell migration capacity. Moreover, miR-326 attenuated ZNF322A-induced tumor growth and lung tumor metastasis in vivo. Clinically, the expression of miR-326 negatively correlated with ZNF322A mRNA expression in surgically resected tissues from 120 non-small cell lung cancer (NSCLC) patients. Multivariate Cox regression analysis demonstrated that NSCLC patients with low miR-326/high ZNF322A profile showed poor overall survival. Our results reveal that the deregulated expression of miR-326 leads to hyperactivation of ZNF322A-driven oncogenic signaling. Targeting the miR-326/ZNF322A axis would provide new therapeutic strategies for lung cancer patients.
關聯:	Biofactors, v.50, n.1, pp.214-227
Appears in Collections:	[通識教育中心] 期刊論文

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