Abstract
Despite advances in diagnosis and treatment, the survival of non-small cell lung cancer (NSCLC) patients remains poor; therefore, improved understanding of the disease mechanism and novel treatment strategies are needed. Downregulation of SMAD4 and dysregulated expression of miR-205 have been reported. However, the relationship between them remains unclear. We investigated the effect of microRNA (miR)-205 on the expression of SMAD4 in NSCLC. Knockdown and overexpression of SMAD4 promoted or suppressed cellular viability and proliferation, and accelerated or inhibited the cell cycle in NSCLC cells, respectively. The 3′-untranslated region (3′-UTR) of SMAD4 was predicted as a target of miR-205. Luciferase assays validated that miR-205 binds directly to the SMAD4 3′-UTR. Protein and mRNA expression analyses confirmed that miR-205 overexpression in NSCLC cells inhibited the expression of SMAD4 mRNA and protein. In human NSCLC tissues, increased miR-205 expression was observed frequently and was inversely correlated with decreased SMAD4 expression. Ectopic expression of miR-205 in NSCLC cells suppressed cellular viability and proliferation, accelerated the cell cycle, and promoted tumor growth of lung carcinoma xenografts in nude mice. Our study showed that miR-205 decreased SMAD4 expression, thus promoting NSCLC cell growth. Our findings highlighted the therapeutic potential of targeting miR-205 in NSCLC treatment.
Highlights
Worldwide, lung cancer is a primary cause of cancer-related death [1], and among lung cancer patients, more than 80 percent have non-small cell lung cancer (NSCLC)
The results showed that SMAD4 mRNA levels were significantly lower in NSCLC tissues than in adjacent noncancerous lung tissues (Figure 1A)
We found higher SMAD4 expression in adenocarcinomas compared with other types of NSCLC (P = 0.02)
Summary
Lung cancer is a primary cause of cancer-related death [1], and among lung cancer patients, more than 80 percent have non-small cell lung cancer (NSCLC). Stage diagnosis and surgery of NSCLC pateints could result in a 5-year survival rate of up to 55–80% [2]. A better understanding of the mechanisms of NSCLC development and progression are important for early diagnosis and prevention, as well as targeted treatment. MiRNAs have important effects on diverse biological and pathological processes, including tumor cell proliferation, differentiation, and survival [6,7,8]. Dysregulation of miR-205 was observed in many types of tumors, including lung cancer [12]. Another study showed that low miR-205 expression in mammary epithelial cells promoted EMT, while its overexpression repressed cancer cells stemness [14]. The expression of miR-205 was higher in squamous cell lung carcinoma compared with other types of NSCLC [10]
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