hsa-miR-CHA2, a novel microRNA, exhibits anticancer effects by suppressing cyclin E1 in human non-small cell lung cancer cells

• Published in: Biochimica et biophysica acta. Molecular basis of disease 2024-08, Vol.1870 (6), p.167250, Article 167250
• Main Authors: Lee, So Jeong, Jeon, Seong Ho, Cho, Sinyoung, Kim, Chang Min, Yoo, Jung Ki, Oh, Seung-Hun, Kim, Jong Hyup, Yang, Young Duk, Kim, Jin Kyeoung
• Format: Article
• Language: English
• Subjects: CCNE1; Cell cycle; Human NSCLC; Novel microRNA; Proliferation
• ISSN: 0925-4439; 1879-260X; 1879-260X
• DOI: 10.1016/j.bbadis.2024.167250

Despite considerable therapeutic advancements, the global survival rate for lung cancer patients remains poor, posing challenges in developing an effective treatment strategy. In many cases, microRNAs (miRNAs) exhibit abnormal expression levels in cancers, including lung cancer. Dysregulated miRNAs often play a crucial role in the development and progression of cancer. Therefore, understanding the mechanisms underlying aberrant miRNA expression during carcinogenesis may provide crucial clues to develop novel therapeutics. In this study, we identified and cloned a novel miRNA, hsa-miR-CHA2, which is abnormally downregulated in non-small cell lung cancer (NSCLC)-derived cell lines and tissues of patients with NSCLC. Furthermore, we found that hsa-miR-CHA2 regulates the post-transcriptional levels of Cyclin E1 (CCNE1) by binding to the 3′-UTR of CCNE1 mRNA. CCNE1, a cell cycle regulator involved in the G1/S transition, is often amplified in various cancers. Notably, hsa-miR-CHA2 overexpression led to the alteration of the Rb-E2F pathway, a significant signaling pathway in the cell cycle, by targeting CCNE1 in A549 and SK-LU-1 cells. Subsequently, we confirmed that hsa-miR-CHA2 induced G1-phase arrest and exhibited an anti-proliferative effect by targeting CCNE1. Moreover, in subcutaneous xenograft mouse models, intra-tumoral injection of polyplexed hsa-miR-CHA2 mimic suppressed tumor growth and development. In conclusion, hsa-miR-CHA2 exhibited an anticancer effect by targeting CCNE1 both in vitro and in vivo. These findings suggest the potential role of hsa-miR-CHA2 as an important regulator of cell proliferation in molecular-targeted therapy for NSCLC. [Display omitted] •The novel microRNA, hsa-miR-CHA2, is abnormally down-regulated in Non-Small Cell Lung Cancer (NSCLC).•The hsa-miR-CHA2 directly targets Cyclin E1 (CCNE1), a key regulator of cell cycle processes in the G1/S transition.•The hsa-miR-CHA2 induces G1-phase arrest and inhibits cell proliferation in NSCLC cells.•The hsa-miR-CHA2 exhibits an anticancer effect during tumorigenesis in subcutaneous xenograft in vivo models.