Abstract
BackgroundIn South China (Gejiu City, Yunnan Province), lung cancer incidence and associated mortality rate is the most prevalent and observed forms of cancer. Lung cancer in this area is called Gejiu squamous cell lung carcinoma (GSQCLC). Research has demonstrated that overexpression of miR-21 occurs in many cancers. However, the unique relationship between miR-21 and its target genes in GSQCLC has never been investigated. The molecular mechanism involved in GSQCLC must be compared to other non-small cell lung cancers in order to establish a relation and identify potential therapeutic targets.Methodology/Principal FindingsIn the current study, we initially found overexpression of miR-21 occurring in non-small cell lung cancer (NSCLC) cell lines when compared to the immortalized lung epithelial cell line BEAS-2B. We also demonstrated that high expression of miR-21 could increase tumor cell proliferation, invasion, viability, and migration in GSQCLC cell line (YTMLC-90) and NSCLC cell line (NCI-H157). Additionally, our results revealed that miR-21 could suppress YTMLC-90 and NCI-H157 cell apoptosis through arresting cell-cycle at G2/M phase. Furthermore, we demonstrated that PTEN, RECK and Bcl-2 are common target genes of miR-21 in NSCLC. Finally, our studies showed that down-regulation of miR-21 could lead to a significant increase in PTEN and RECK and decrease in Bcl-2 at the mRNA and protein level in YTMLC-90 and NCI-H157 cell lines. However, we have not observed any remarkable difference in the levels of miR-21 and its targets in YTMLC-90 cells when compared with NCI-H157 cells.Conclusions/SignificancemiR-21 simultaneously regulates multiple programs that enhance cell proliferation, apoptosis and tumor invasiveness by targeting PTEN, RECK and Bcl-2 in GSQCLC. Our results demonstrated that miR-21 may play a vital role in tumorigenesis and progression of lung squamous cell carcinoma and suppression of miR-21 may be a novel approach for the treatment of lung squamous cell carcinoma.
Highlights
Lung cancer is the most common cause of cancer-related death worldwide [1]
To understand whether the expression of miR-21 was correlated with the malignancy of Gejiu squamous cell lung carcinoma (GSQCLC), we first evaluated the expression level of miR-21 in human Non-small cell lung carcinoma (NSCLC) cell lines A549, National Cancer Institute (NCI)-H157, NCI-H460, H460SM, YTMLC-90, XWLC-05 and GLC, compared to an immortalized lung epithelial cell line BEAS2B [38]
The results showed miR-21 down-regulation by pGCMV/EGFP-hsa-miR-21 interference plasmid at 48 h post-transfection significantly resulted in the increase of PTEN and RECK gene expression, and the reduction of B-cell lymphoma 2 (Bcl-2) gene expression in YTMLC-90 and NCI-H157 cells at mRNA level (p,0.05, p,0.01) (Fig. 3A) or protein level (p,0.05, p,0.01) (Fig. 3B, Fig. S3 in File S1)
Summary
Lung cancer is the most common cause of cancer-related death worldwide [1]. Despite years of research, the prognosis for patients with lung cancer remains dismal. Lung cancer in this area is called Gejiu squamous cell lung carcinoma (GSQCLC). In South China (Gejiu City, Yunnan Province), lung cancer incidence and associated mortality rate is the most prevalent and observed forms of cancer. The molecular mechanism involved in GSQCLC must be compared to other non-small cell lung cancers in order to establish a relation and identify potential therapeutic targets
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