MiR‐138‐5p suppresses the progression of lung cancer by targeting SNIP1

Abstract

Background MicroRNAs (miRNAs) play crucial roles in the development of various cancers. Here, we aimed to evaluate the roles of miR‐138‐5p in lung cancer progression and the value of miR‐138‐5p in lung cancer diagnosis. Methods Quantitative real‐time PCR was performed to examine the expressions of miR‐138‐5p and smad nuclear interacting protein 1 (SNIP1) mRNA. The diagnostic value of miR‐138‐5p was analyzed using receiver operating characteristic (ROC) curve analysis, sensitivity, and specificity. We explored the effect of miR‐138‐5p on cell proliferation and metastasis by CCK‐8, colony formation, wound healing and transwell assays. Western blot was employed to detect the protein expression of SNIP1 and related genes. Lung cancer cell growth was evaluated in vivo using xenograft tumor assay. Results MiR‐138‐5p was decreased in the serum of patients with non‐small cell lung cancer (NSCLC) and in NSCLC cells and tissues. The area under the ROC curve of serum miR‐138‐5p in the diagnosis of NSCLC was 0.922. This finding indicates the high diagnostic efficiency for lung cancer. MiR‐138‐5p suppressed but its inhibitor promoted cell proliferation and migration compared with control treatment in vitro and in vivo. MiR‐138‐5p directly binds to the 3′‐untranslated region of SNIP1 and negatively regulated the expression of SNIP1, thereby inhibiting the expression of cyclin D1 and c‐Myc. Moreover, overexpression of SNIP1 rescues the miR‐138‐5p‐mediated inhibition in NSCLC cells. Conclusions The results suggested that miR‐138‐5p suppressed lung cancer cell proliferation and migration by targeting SNIP1. Serum miR‐138‐5p is a novel and valuable biomarker for NSCLC diagnosis.

Extracellular circulating miRNAs as potential non-invasive biomarkers in non-small cell lung cancer patients

“…MiR-138-5p was found under-expressed in NSCLC cell lines (A549, H1975, and PC9), serum and lung ADC tissues. NSCLC could be distinguished accurately from healthy controls by miR-138-5p with an AUC of 0.922, which supports this miRNA potential utility in NSCLC diagnosing (90). In another study, microarray analysis of miRNA from four NSCLC patients and five healthy subjects helped to select miR-1247-5p, miR-301b-3p, and miR-105-5p.…”

The clinical utilization of SNIP1 and its pathophysiological mechanisms in disease

“…The suppression of SNIP1 expression in NSCLC cells by miR-138-5p has been found to impede the expression of full-length SNIP1 or its amino terminus [ 28 ].What is more, SNIP1 is a non-histone substrate of lysine methyltransferase KMT5A, which undergoes KMT5A-mediated mono-methylation to promote breast cancer cell growth and invasion. KMT5A-mediated K301 methylation of SNIP1 inhibits the hippo protein kinase cascade through transcriptional activation of Mark 4, enhancing the metastasis of triple-negative breast cancer (TNBC) [ 29 ].…”

“…What is more, miR-138-5p suppressed lung cancer cell proliferation and migration by targeting SNIP1. [ 28 ] Triple-negative breast cancer (TNBC) Mass spectrometry (MS) analysis to identify KMT5A. Coimmunoprecipitation assay and LC-MS/MS analysis SNIP1-interacting proteins from MDA-MB-231 cells.…”

Liquid Biopsy in non-small cell lung cancer: exosomes as a tool for the study of biomarkers.

“…Specifically, in NSCLC it is possible that miR-138 plays a suppressive role in growth and metastasis [282,283]. In patient serum samples, this miRNA has already shown evidence of being a novel and valuable biomarker for the diagnosis of NSCLC [283]. However, the confirmation of their presence in NSCLC exosomes by our work would mean that the biomarkers present in these microvesicles would have greater protection in the bloodstream.…”

“…In addition, the effects of miR-138 have also been identified as a promising prognostic biomarker and therapeutic target for oral squamous cell carcinoma with metastatic potential [281]. Specifically, in NSCLC it is possible that miR-138 plays a suppressive role in growth and metastasis [282,283]. In patient serum samples, this miRNA has already shown evidence of being a novel and valuable biomarker for the diagnosis of NSCLC [283].…”