Inhibition mechanism of lung cancer cell metastasis through targeted regulation of Smad3 by miR‑15a

Abstract

Effect of targeted regulation of mothers against decapentaplegic homolog 3 (Smad3) by microRNA-15a (miR-15a) on the proliferation, invasion and metastasis of non-small cell lung cancer (NSCLC) cells and its related mechanisms were investigated. Fifty pairs of NSCLC and para-cancerous tissues were collected to identify the expression level of miR-15a in NSCLC, para-cancerous tissue, and cell lines A549, H1299, H1975 and BEAS-2B by real-time fluorescence quantitative PCR (RT-PCR); A549 cells were transfected with miR-15a mimic; the MTT assay was performed to detect the role of miR-15a transfection in proliferation of A549 cells, the wound healing assay was carried out to identify the role of miR-15a in migration of A549 cells; Transwell invasion assay was conducted to analyze the role of miR-15a in invasion of A549 cells; western blotting was carried out to find the effect of miR-15a on Smad3 expression, and Spearman's rank correlation was used to analyze the correlation between miR-15a and Smad3 expression. NSCLC tissues and cells showed significantly lower miR-15a expression, compared with para-cancerous tissues and normal cell lines (P=0.023). miR-15a was significantly more expressed in A549 cells transfected with miR-15a mimic (P=0.043). Overexpression of miR-15a can significantly inhibit A549 cell proliferation (P=0.038), migration (P=0.033) and invasion (P=0.025), and significantly reduced the expression level of Smad3 (P=0.031) in A549 cells. Spearman's rank correlation showed negative correlation of miR-15a expression with Smad3, which may indicate negative regulation (r=-0.34, P<0.0001). Inhibition of proliferation, migration and invasion of NSCLC cells can be achieved with targeted regulation of Smad3 by miR-15a.

WITHDRAWN: Stromal Cell-Derived Factor 1 Secreted by Cancer- Associated Fibroblasts Promotes lncRNA Xist through CXCR4 and Facilitates Invasion and Metastasis of Non-Small Cell Lung Cancer

“…After coculture with CAFs, miR-15a-5p was also upregulated in CAFs + mimic group, the invasion and migration were decreased, E-cadherin was increased and N-cadherin was decreased, and MMP3 was reduced. Overexpression of miR-15a can signi cantly inhibit A549 cell proliferation, migration and invasion [41,42]. Collectively, overexpression of miR-15a-5p can reduce the promotion of SDF-1 secreted by CAFs on NSCLC.…”

Non-coding RNAs in necroptosis, pyroptosis and ferroptosis in cancer metastasis

“…Necroptosis was induced through lncRNA3037/miR-15a/BCL2-A20 signaling pathway [ 24 ]. miR-15a inhibits the growth and metastasis of human cancers by regulating Stat3 [ 135 ], Smad3 [ 136 ], Twist1 [ 137 , 138 ], CXCL10 [ 139 ], etc. LncRNA-107053293 miR-148a-3p LncRNA-107053293 regulated necroptosis by acting as a ceRNA of miR-148a-3p [ 25 ].…”

Alpha‐2‐Heremans‐Schmid‐glycoprotein (AHSG) a potential biomarker associated with prognosis of chromophobe renal cell carcinoma: The PROPOLIS study

“…The result showed that the top 20 proteins interacting with AHSG (Figure 9B ) mainly functioned in tumor suppressor, signal transduce, cancer development. 26 , 27 , 29 , 30 , 33 , 34 , 35 , 36 , 37 , 38 , 39…”