Background: The role of microRNA-133a (miR-133a) in non-small cell lung cancers (NSCLCs) is controversial. Thus, we conducted a comprehensive study based on meta-analysis and The Cancer Genome Atlas (TCGA) database. Methods: Publications were searched in both English and Chinese databases, and meta-analysis was performed using Stata 12.0. The clinical value of miR-133a in NSCLC was investigated by collecting and calculating data from the TCGA database, and the statistical analysis was performed in R 3.5.0. Results: 5 studies with 364 cases were included in this meta-analysis. The combined pooled result showed that high expression of miR-133a was associated with a favorable survival outcome in NSCLC patients (hazard ratio 0.561, 95% confidence interval 0.396-0.794, p = 0.001). Meanwhile, a total of 984 NSCLC patients were extracted from the TCGA database. Results showed an area under the ROC curve value for miR-133a-3p of 0.902, and the expression of miR-133a-3p was linked with clinicopathologic parameters of NSCLC (p < 0.05), including sex, age, social status, and lymph node metastasis. Conclusion: Our study indicated that miR-133a might act as a tumor suppressor and be a valuable independent prognostic and diagnostic biomarker for NSCLC, and NSCLC patients with high expression of miR-133 might have a better prognosis.
Ras‐association domain family 1A (RASSF1A) is one of the most methylated genes in lung cancer (LC). We investigate whether the high DNA methylation level of RASSF1A can relieve the resistance of RASSF1A to LC by inhibiting RASSF1A's transcription factor binding to RASSF1A. RASSF1A expression in tissues and cells was tested utilizing quantitative real‐time polymerase chain reaction (qRT‐PCR), and Western blot. RASSF1A expression and RASSF1A methylation level in LC cells exposed to 5‐Aza‐dc were assessed by qRT‐PCR and quantitative methylation‐specific PCR. The association between CTCF and RASSF1A was assessed using hTFtarget, ChIP, and luciferase reporter gene analysis. The effects of 5‐Aza‐dc, CTCF, and RASSF1A on cell biological behaviors and epithelial‐mesenchymal transition (EMT)‐related markers were assessed by cell function experiments and Western blot. Moreover, we constructed the xenograft tumor and pulmonary nodule metastasis models, and assessed tumor volume and weight. RASSF1A expression and pulmonary nodule metastasis were tested utilizing qRT‐PCR, Western blot, and H&E staining. RASSF1A was under‐expressed in LC tissues and cells. 5‐Aza‐dc enhanced RASSF1A level and weakened RASSF1A methylation level in LC cells. RASSF1A silencing neutralized 5‐Aza‐dc‐mediated repressing effects on LC cell biological function and EMT. The loss of CTCF binding to RASSF1A in LC cells was associated with DNA methylation. The effect of 5‐Aza‐dc on RASSF1A level, LC cell malignant behaviors, and EMT‐related factors were strengthened by CTCF upregulation. RASSF1A overexpression suppressed LC tumor growth and pulmonary nodule metastasis in vivo. DNA methylation blocked the modulation of RASSF1A expression by CTCF and relieved the resistance of RASSF1A to LC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.