Promoter A1312C mutation leads to microRNA-7 downregulation in human non-small cell lung cancer

In this study, based on clinical sample analysis, we found that the downregulated expression of miR-7 was dominantly attributed to the decreased level of pri-miR-7-2 in human NSCLC. Furthermore, there were four site mutations in the miR-7-2 promoter sequence. Notably, among these four sites, mutation at -1312 locus (A → C, termed as A1312C mutation) was dominate, and A1312C mutation further led to decreased expression of miR-7 in human NSCLC cells, accompanied with elevated transduction of NDUFA4/ERK/AKT signaling pathway. Mechanistically, homeobox A5 (HOXA5) is the key transcription factors regulating miR-7 expression in NSCLC. A1312C mutation impairs HOXA5 binding, thereby reducing the transcriptional activity of miR-7-2 promoter, resulting in downregulation of miR-7 expression. Together, these data may provide new insights into the dysregulation of specific miRNA expression in NSCLC and ultimately prove to be helpful in the diagnostic, prognostic, and therapeutic strategies against NSCLC.PMID:38346527 | DOI:10.1016/j.cellsig.2024.111095

Source: Cellular Signalling - February 12, 2024 Category: Cytology Authors: Shipeng Chen Hui Wang Mengmeng Guo Xu Zhao Jing Yang Longqing Chen Juanjuan Zhao Chao Chen Ya Zhou Lin Xu Source Type: research