Semaphorin3A Knockdown Upregulates miR-20b-5p to Suppress Cyclin D1 expression and Cell Proliferation in High Bone-Metastatic Lung Cancer Cell

Abstract

Lung cancer remains the leading cause of cancer-related mortality worldwide. In advanced lung cancer stages, bone metastasis is rampant and significantly reduces the quality of life of patients. Members of the semaphorin family, particularly semaphorin 3A (SEMA3A), have been implicated in lung cancer growth and metastasis; however, their role remains unclear. In this study, we investigated the relationship between SEMA3A signaling and microRNA (miRNA) regulation in a highly bone metastatic lung cancer cell line (HARA-B4). Microarray analysis and qRT-PCR revealed upregulation of miR-20b-5p expression in SEMA3A knockdown cells. Target pathway analysis identified cyclin D1(CCND1), a key regulator of cell cycle progression, as the downstream target. miR-20b-5p mimic reduced CCND1 expression and suppressed cell proliferation in HARA-B4. These findings suggest that SEMA3A-dependent tumor growth is mediated by the increased CCND1 expression resulting from reduced miR-20b-5p expression. Understanding the dual roles of SEMA3A and miR-20b-5p may provide potential therapeutic and diagnostic avenues for treating metastatic bone lung cancer.