MicroRNA‑138 suppresses cell proliferation and invasion of renal cell carcinoma by directly targeting SOX9

Abstract

Abstract. An accumulating number of studies have reported that the expression levels of microRNAs (miRNAs/miRs) are dysregulated in a variety of human cancer types, including renal cell carcinoma (RCC). miRNAs play essential functions in tumorigenesis and the progression of tumors by serving as oncogenes or tumor suppressors. Recently, the expression and functions of miR-138 have been studied in a number of human cancer types; however, its role in RCC remains poorly understood. In the present study, the results revealed that miR-138 was significantly downregulated in RCC cell lines and tissues, and that low expression levels of miR-138 were correlated with histological grade, tumor stage and lymph node metastasis. In functional studies, restoration of miR-138 expression inhibited cell proliferation and invasion of ACHN and A498 cells. In addition, SOX9 was validated as a direct target gene of miR-138 in RCC. SOX9 knockdown inhibited cell proliferation and invasion of RCC, with a similar effect to that induced by miR-138, rendering SOX9 a functional target of miR-138 in the disease. These findings indicate that miR-138 may present a novel target for therapeutic strategies in RCC.

miR-4429Inhibits Tumor Progression and Epithelial-Mesenchymal Transition Via TargetingCDK6in Clear Cell Renal Cell Carcinoma

“…3,4 Despite mounting effort in improving diagnosis and treatments for ccRCC through identifying molecular biomarkers, those eligible to serve as successful prognosis and therapeutic targets remains rare. [5][6][7] Hence, it is of critical importance to recognize new targets via molecular mechanism research in ccRCC. The role of miRNAs has caught increasing attention of the researchers.…”

“…4 Although multiple molecular biomarkers have been explored by mounting studies in ccRCC, few of them are able to serve as effective prognostic and therapeutic targets. [5][6][7] Therefore, identification of novel targets through molecular mechanism research in ccRCC is urgent. microRNAs (miRNAs), recognized as an endogenous and conserved cluster of small noncoding RNAs, have been proved to modulate gene expression negatively via targeting the 3¢untranslated region (3¢-UTR) of messenger RNAs (mRNAs).…”

Knockdown of long non-coding RNA PVT1 induces apoptosis and cell cycle arrest in clear cell renal cell carcinoma through the epidermal growth factor receptor pathway

“…To date, several pathological and clinical features have been used to predict patient prognosis, including tumor size, pathological stage, tumor stage, performance status, localized symptoms and cachexia ( 3 ). However, few molecular biomarkers exist that may predict patient prognosis and serve as therapeutic targets, although numerous molecular biomarkers have been investigated in ccRCC ( 4 – 5 ). Previous studies have highlighted the mutations of BRCA1 associated protein-1 and SET domain containing 2, which are inversely correlated with the outcome of patients with ccRCC ( 6 – 8 ).…”

MicroRNA-138-5p Suppresses Non-small Cell Lung Cancer Cells by Targeting PD-L1/PD-1 to Regulate Tumor Microenvironment

“…The expression of miR-138 is reduced in various cancers, including anaplastic thyroid carcinoma (ATC), NSCLC, gallbladder carcinoma, and oral squamous cell carcinoma (OSCC) ( Xu et al, 2015 ; Ye et al, 2015 ; Li et al, 2016 ; Hu et al, 2017 ; Si et al, 2017 ; Liu et al, 2018 ). In agreement, miR-138 overexpression can significantly inhibit tumor cell proliferation ( Zhang et al, 2013 ; Li et al, 2015 ; Ye et al, 2015 ; Han et al, 2016 ).…”

“…MiR-138 has been reported to play a suppressive role in certain common types of human cancer, including brain cancer, osteosarcoma, cervical cancer, larynx carcinoma, and lung cancer, and so on ( Sha et al, 2017 ; Yeh et al, 2019 ), and is considered to be a promising therapeutic target for cancer. The suppressive function of miR-138 was found to target enhancer of zeste homolog 2 (EZH2) ( Zhang et al, 2013 ; Si et al, 2017 ), pyruvate dehydrogenase kinase 1 and G protein-coupled receptor 124 (GPR124) ( Gao et al, 2014 ; Ye et al, 2015 ), SP1 ( Liu et al, 2018 ), SOX9 ( Hu et al, 2017 ), and cyclin D3 ( Huang et al, 2015 ) to inhibit tumor cell growth and migration. Although some studies showed that over-expression of miR-138 in CD4 + T cells from psoriasis patients decreased the amounts of Th1/Th2 cells ( Fu et al, 2015 ), and miR-138 in T cells also targeted PD-1 and CTLA-4 to regulate T cell tolerance ( Wei et al, 2016 ).…”