MiR‐490‐5p inhibits the stemness of hepatocellular carcinoma cells by targeting ECT2

Abstract

To explore the targeting relationship between miR-490-5p and ECT2 in hepatocellular carcinoma (HCC) and the influences of miR-490-5p and ECT2 on the stemness of HCC cells. The expressions of miR-490-5p and ECT2 in HCC tissues and adjacent tissues were identified by quantitative real-time polymerase chain reaction (qRT-PCR). The relationships between the expression levels of miR-490-5p/ ECT2 and the overall/disease-free survival (OS/DFS) of patients with HCC were evaluated using correlative curves. In addition, the targeting relationship between miR-490-5p and ECT2 was predicted by TargetScan and verified by dual-luciferase reporter assay. Plasmid transfection was used for overexpression of ECT2 in HepG2 cells, and transfection efficiency was verified by qRT-PCR. Cell Counting Kit-8 assay and cell sphere-formation assay were conducted to detect the proliferation and sphere-formation ability of HCC cells, respectively. Cell populations with different cell transfections were sorted using flow cytometry. The expression levels of proteins in the stem cell signaling pathway were determined using Western blot analysis. MiR-490-5p was remarkably downregulated, yet ECT2 was upregulated in HCC tissues compared with adjacent tissues. MiR-490-5p expression was positively correlated with OS and DFS of patients with HCC, which were otherwise negatively correlated with ECT2 expression. ECT2 was validated to be the downstream target of miR-490-5p. Overexpression of miR-490-5p restrained the sphere formation ability, stemness, and proliferation of HCC cells. MiR-490-5p repressed the stemness of HCC cells through inhibiting the expression of ECT2. MiR-490-5p may be an underlying therapeutic target in HCC treatment.

ECT2 overexpression promotes the polarization of tumor-associated macrophages in hepatocellular carcinoma via the ECT2/PLK1/PTEN pathway

“…The activation of the ECT2/Rho pathway may promote the progression of several tumors 7 . ECT2 may promote the progression of human HCC by regulating the Rho/ ERK signaling axis [8][9][10] . ECT2 also plays a tumorpromoting role in a number of other cancers, such as non-small cell lung cancer and breast cancer [11][12][13][14] .…”

Clinicopathological and prognostic significance of epithelial cell transforming sequence 2 expression in cancers: a systematic review and meta-analysis

“…Substantial evidence favours the notion that miRNAs regulate cancer progression, and several studies have suggested that some miRNAs regulates tumour progression by targeting ECT2. For instance, Yu et al [17] and Fang et al [54] have shown that MiR-490-5p could repress the metastasis and stemness of hepatocellular carcinoma cells by downregulating ECT2 expression. Xu et al [55] have reported that the downregulation of ECT2 by miR-223 induces the expression of p21 and p27, which restrain cell cycle progression and proliferation in osteosarcoma cells.…”

“…Accordingly, the aberrant overexpression of ECT2 may have protumorigenic effects. Indeed, growing evidence suggests that ECT2 is frequently overexpressed in various cancers and serves as an oncogene [15][16][17][18]. Moreover, numerous clinical studies have shown that high ECT2 expression is associated with adverse clinicopathological characteristics, such as poor tumour differentiation, larger tumour size, positive lymphatic metastasis, and advanced disease stage, and as well as an unfavourable prognosis in multiple type of cancers [11,15,[19][20][21][22][23][24][25], further suggesting that it is a promising prognostic biomarker in cancers.…”

miR‐490: A potential biomarker and therapeutic target in cancer and other diseases

“…Besides miR‐490‐3p, low levels of miR‐490‐5p have been associated with a poor outcome in hepatocellular carcinoma (overall survival and disease‐free survival and correlated with lymph node metastasis, primary tumor stage, TNM stage, the recurrence rate at early TNM stage, age, tumor size, alpha‐fetoprotein, hepatitis B antigen, and portal vein thrombosis; Fang et al, 2018; Xu et al, 2017; Yu et al, 2019), neuroblastoma (overall survival and correlation with grade and lymph node metastasis; J. Wang et al, 2020) and pharyngolaryngeal cancer (overall survival; Abdeyrim et al, 2019). Also, miR‐490 downregulation has been correlated with disease progression in hepatocellular carcinoma (Ding et al, 2020; P. Wu et al, 2019) and non‐small cell lung cancer (Dong et al, 2020).…”