7‑Difluoromethoxyl‑5,4'‑di‑n‑octylygenistein targets the STAT3 pathway by upregulating microRNA‑152‑3p expression to inhibit self‑renewal and tumor growth in non‑small cell lung carcinoma

MicroRNAs (miRs) serve a pivotal role in the regulation of non‑small cell lung carcinoma (NSCLC). The present study aimed to investigate the antitumor effects of 7‑difluoromethoxyl‑5,4'‑di‑n‑octylygenistein (DFOG), a novel synthetic genistein derivative, on NSCLC, and to elucidate its molecular mechanism. The research focused on whether DFOG inhibited self‑renewal and tumor growth in NSCLC by modulating the miR‑152‑3p/STAT3 signaling pathway. Reverse transcription‑quantitative PCR and western blot analyses were employed to assess miR‑152‑3p expression and phosphorylated‑STAT3 (p‑STAT3) levels. The effects of DFOG on self‑renewal and tumor growth were evaluated via sphere formation and clonogenic assays. Additionally, sphere‑forming cells (SFCs) were enriched using a suspension culture method, and western blot analysis was conducted to examine stemness markers (CD133, CD44, Oct4 and Sox2). The results demonstrated that DFOG inhibited self‑renewal and tumor growth in NSCLC. This effect was associated with increased miR‑152‑3p expression, decreased STAT3 mRNA levels and reduced p‑STAT3 levels in NSCLC cells. Furthermore, inhibition or overexpression of STAT3 did not alter miR‑152‑3p expression but modulated the inhibitory effects of DFOG on self‑renewal and tumor growth. These findings highlighted that DFOG suppressed self‑renewal and tumor growth in SFCs derived from NSCLC by directly targeting STAT3 through the upregulation of miR‑152‑3p.