miR-138 suppresses the proliferation, metastasis and autophagy of non-small cell lung cancer by targeting Sirt1

Abstract

The present study determined the role and mechanism of miR-138 in non-small cell lung cancer (NSCLC). In total, 45 freshly resected clinical NSCLC tissues were collected. The expression of miR-138 in tissues and cell lines were determined by real-time quantitative PCR. miR-138 mimics were transfected into A549 and Calu-3 cells in vitro, and then the effects of miR-138 on lung cancer cell proliferation, cell cycle, invasion and metastasis were investigated by CCK-8 assay, Transwell and flow cytometry, respectively. The protein expression of the potential target gene Sirt1 in lung cancer cells were determined by western blot analysis. Dual-Luciferase reporter assay was performed to further confirm whether Sirt1 was the target gene of miR-138. The expression of miR-138 was significantly lower in lung cancer tissues and was negatively correlated to the differentiation degree and lymph node metastasis of lung cancer. In vitro experiment results showed that miR-138 inhibited lung cancer cell proliferation, invasion and migration. It was verified that miR-138 could downregulate Sirt1 protein expression, inhibit epithelial-mesenchymal transition (EMT), decrease the activity of AMPK signaling pathway and elevate mTOR phosphorylation level. Dual-Luciferase reporter assay demonstrated that miR-138 could directly regulate Sirt1. Downregulation of Sirt1 alone can also cause the same molecular and biological function changes. Western blot analysis and confocal microscopy results indicated that overexpression of miR-138 or interference of Sirt1 expression could inhibit lung cancer cell autophagy activity possibly through AMPK-mTOR signaling pathway. miR-138 plays a tumor suppressor function in lung cancer. It may inhibit the proliferation, invasion and migration of lung cancer through downregulation of Sirt1 expression and activation of cell autophagy. The downregulation of miR-138 is closely related to the development of lung cancer.

RETRACTED ARTICLE: MicroRNA-183 affects the development of gastric cancer by regulating autophagy via MALAT1-miR-183-SIRT1 axis and PI3K/AKT/mTOR signals

“…Qiu et al also revealed that SIRT1autophagy axis could be used as a prognostic indicator in GC [30]. Moreover, miR-138 is found to inhibit lung cancer cell proliferation and metastasis via downregulation of SIRT1 and activation of cell autophagy [31]. In our study, knockdown of SIRT1 changeover the impacts of depression of miR-183 alone on SGC-7901 cell viability, apoptosis and autophagy.…”

MicroRNA-138 Aggravates Inflammatory Responses of Macrophages by Targeting SIRT1 and Regulating the NF-κB and AKT Pathways

“…[42,43]. MiR-138 directly targets SIRT1 in osteosarcoma, non-small cell lung cancer and axon regeneration [16,20,21]. The inhibitor or antagomir of miR-138 protected mice from the inflammatory reaction, tissue damage and organ dysfunction, and the NF-κB pathway was inhibited while the AKT pathway was activated.…”

“…Additionally, we previously showed that SIRT1 regulates the effect of melatonin on kidney protection against inflammation reactions in severely burned rats [19]. Previously study demonstrated that SIRT1 is a direct target of miR-138, participating in cancer and axon regeneration [16,20,21], but whether miR-138 participates in inflammation by targeting SIRT1 is still unclear. In the present study, we provided the first evidence that miR-138 is an important regulator participating in the inflammatory process and the pre-treatment of miR-138 inhibitor showed significantly effect protecting mice from LPS challenge.…”

MicroRNAs: A novel potential biomarker for diagnosis and therapy in patients with non‐small cell lung cancer

“…74 Therefore, in a global sense, dysregulation of miRNA would make some changes in the behaviour of cells and have a tendency to cancerous conditions. A variety of dysregulated miRNAs, which could act as potential diagnostic and therapeutic biomarkers in NSCLC patients, including let-7c, 75 miR-138, [76][77][78] miR-145, 79 miR-183, 80 miR-29 family, 81 miR-34a, 82 miR-34c-3p, 83 miR-101-3p, 84 These results suggested that miR-9600 could play an important role as potential therapeutic biomarkers in NSCLC patients. 100 Integrin subunit beta 1 (ITGB1) is an essential subgroup of the integrin family, which plays an important role in regulating cellextracellular matrix (ECM) adhesion and signalling, affecting various of cellular processes, including cell proliferation, apoptosis, metastasis, invasion and survival.…”