Abstract
The class III histone deacetylase silent information regulator 1 (SIRT1) is frequently overexpressed in a variety of tumors, including lung cancer; however, its regulatory mechanisms are largely unknown. In this study, we found that an inconsistent trend between SIRT1 protein and mRNA levels in human lung cancer tissues, suggesting that a post-transcriptional mechanism may involved in SIRT1 regulation. Because microRNAs are important post-transcriptional regulators of gene expression, candidate miRNAs that could potentially bind SIRT1 were gained through bioinformatics analyses. We further experimentally validated SIRT1 as the direct target of miR-30a by evaluating SIRT1 expression in lung cancer cells after the overexpression or knockdown of miR-30a and by luciferase assay. Moreover, we showed that miR-30a inhibited proliferation, invasion and promoted apoptosis of lung cancer cells by inhibiting SIRT1 in vitro and in vivo. Taken together, this study identified a new regulatory axis in which miR-30a and SIRT1 regulate the proliferation, invasion and apoptosis of lung cancer cells and lung tumorigenesis.
Highlights
Lung cancer is the most frequently diagnosed and leading cause of death cancer worldwide [1], and nonsmall-cell lung cancer (NSCLC) accounts for 75–80% of all cases [2]
We showed that Sirtuin 1 (SIRT1) as a direct target gene of miR-30a, resulting in the downregulation of SIRT1 protein expression
We found that SIRT1 protein levels were consistently upregulated in lung cancer tissues (Figure 1A and 1B)
Summary
Lung cancer is the most frequently diagnosed and leading cause of death cancer worldwide [1], and nonsmall-cell lung cancer (NSCLC) accounts for 75–80% of all cases [2]. Most lung cancer patients are diagnosed with metastatic and advanced disease, and only a small proportion is eligible for surgical resection and radical treatment [3]. New treatment strategies are needed, and further understanding the molecular mechanisms underlying lung carcinogenesis is of major significance and might provide novel strategies for lung cancer treatment. Sirtuins are belong to the class III histone deacetylase (HDAC) family and have been linked to longevity in lower organisms and to mammalian metabolism [4, 5]. SIRT1 plays important roles in numerous processes, including cell cycle, metabolism, DNA repair, aging and cell survival under stress conditions [4, 5]
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