miR-17-5p knockdown inhibits proliferation, autophagy and promotes apoptosis in thyroid cancer via targeting PTEN

Abstract

Thyroid cancer is one common endocrine malignancy with various pathological types. MicroRNAs (miRNAs) play essential roles in development, prognosis and treatment of thyroid cancer. However, the role of miR-17-5p in thyroid cancer progression and its mechanism remain poorly understood. The expressions of miR-17-5p and phosphatase and tensin homolog (PTEN) were measured in thyroid cancer tissues and cells by quantitative real-time polymerase chain reaction or western blot. Cell proliferation and apoptosis were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay and flow cytometry, respectively. The protein levels of biomarkers in autophagy or protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway were analyzed by western blot. The interaction between miR-17-5p and PTEN was probed by luciferase activity assay. We found that miR-17-5p expression was elevated and PTEN level was reduced in thyroid cancer tissues and cells compared with their corresponding controls. Knockdown of miR-17-5p or overexpression of PTEN suppressed cell proliferation and autophagy but promoted apoptosis in thyroid cancer cells. PTEN was indicated as a target of miR-17-5p and its interference reversed abrogation of miR-17-5p-mediated inhibition of proliferation and autophagy and increase of apoptosis. Moreover, downregulation of miR-17-5p impeded the activation of AKT/mTOR pathway in thyroid cancer cells, which was attenuated by silencing PTEN. Our data supported that knockdown of miR-17-5p upregulated PTEN expression, therefore leading to suppression of the malignancy of thyroid cancer and inactivation of AKT/mTOR pathway, providing a novel avenue for treatment of thyroid cancer.

MiR-25-3p targets PTEN to regulate the migration, invasion, and apoptosis of esophageal cancer cells via the PI3K/AKT pathway

“…PTEN, which was identified in 1977, is a classical cancer suppressor and possesses lipid and protein phosphatase activities [28]. In malignant cells, PTEN has been shown to be silenced by the expressions of a number of micro-RNAs and able to drive a transcriptional program that is essential for maintaining the malignant state of diseases, such as cell proliferation, apoptosis, invasion, and adhesion [29,30]. Shi et al reported that PTEN was targeted by miR-17-5p to regulate the proliferation and autophagy of thyroid cancer [30]; Chen et al proved that miR-21 regulated the proliferation and apoptosis of bladder cancer mediated through PTEN [31]; PTEN was also targeted by miR-216a to enhance the proliferation and fibrogenesis of human cardiac fibroblasts [32].…”

“…In malignant cells, PTEN has been shown to be silenced by the expressions of a number of micro-RNAs and able to drive a transcriptional program that is essential for maintaining the malignant state of diseases, such as cell proliferation, apoptosis, invasion, and adhesion [29,30]. Shi et al reported that PTEN was targeted by miR-17-5p to regulate the proliferation and autophagy of thyroid cancer [30]; Chen et al proved that miR-21 regulated the proliferation and apoptosis of bladder cancer mediated through PTEN [31]; PTEN was also targeted by miR-216a to enhance the proliferation and fibrogenesis of human cardiac fibroblasts [32]. Similarly, in the present study, we found that PTEN not only inhibited the migration and invasion, and induced apoptosis of EC cells, but also reversed the effect of miR-25-3p on EC cells, which further confirmed that miR-25-3p regulated the migration, invasion, and apoptosis of EC cells by targeting PTEN.…”

The lncRNA HOTAIR regulates autophagy and affects lipopolysaccharide‐induced acute lung injury through the miR‐17‐5p/ATG2/ATG7/ATG16 axis

“…Interestingly, previous studies reported that miR‐17‐5p regulates autophagy in several diseases. 33 , 34 Bobbili et al 35 described miR‐17‐5p as an essential regulator of autophagy and an ‘alarm signal’ in cancer. We observed a negative association between miR‐17‐5p and autophagy, as si‐HOTAIR suppressed autophagosome formation in LPS‐stimulated A549 and BEAS‐2B cells, whereas miR‐17‐5p inhibition upregulated ATG2, ATG7, and ATG16 protein expression.…”

Small in Size, but Large in Action: microRNAs as Potential Modulators of PTEN in Breast and Lung Cancers

“…Notably, numerous studies have shed light on the relationship between miRNAs and PTEN. Apoptosis, autophagy, and proliferation of cancer cells are affected by miRNAs in different cancers [102,103]. As miRNAs are well-known regulators in cancer cells, understanding their impact on PTEN expression can be beneficial in providing novel therapeutics.…”