miR-23b-3p Inhibits the Oncogenicity of Colon Adenocarcinoma by Directly Targeting NFE2L3

Abstract

Background and Aims. MicroR-23b-3p (miR-23b-3p) has been found to be abnormally expressed in a variety of malignant tumors and to play a role in tumor inhibition or promotion. However, the regulatory mechanism of miR-23b-3p in COAD remains unclear. The purpose of this study was to investigate the clinical significance of miR-23b-3p expression in COAD cells and to explore its role and regulatory mechanism in the growth of COAD. Materials and Methods. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure miR-23b-3p expression in COAD tissues and cell lines. After transfecting miR-23b-3p mimics into two human COAD cell lines (SW620 and LoVo), the cell counting kit-8 (CCK-8), colony formation, and 5-ethynyl-2′-deoxyuridine (EdU) assays were used to detect cell proliferation, the Transwell assay was used to measure cell migration and invasion capacity, and flow cytometry was used to evaluate cell apoptosis in vitro. In addition, a luciferase reporter assay was used to determine whether miR-23b-3p targets NFE2L3. The downstream regulatory mechanisms of miR-23b-3p action in COAD cells were also investigated. For in vivo tumorigenesis assay, COAD cells stably overexpressing miR-23b-3p were injected subcutaneously into the flank of nude mice to obtain tumors. Results. Significantly decreased expression of miR-23b-3p was detected in COAD tissues and cell lines. Exogenous miR-23b-3p expression inhibited cell proliferation, migration, and invasion and promoted cell apoptosis of COAD cells in vitro. Nuclear factor erythroid 2 like 3 (NFE2L3) was identified as a direct target gene of miR-23b-3p. In addition, reintroduction of NFE2L3 partially abolished the anticancer effects of miR-23b-3p on COAD cells. Furthermore, miR-23b-3p overexpression hindered the growth of COAD cells in vivo. Conclusion. miR-23b-3p inhibited the oncogenicity of COAD cells in vitro and in vivo by directly targeting NFE2L3, suggesting the importance of the miR-23b-3p/NFE2L3 pathway in the development of COAD.

Advances in the Biological Functions and Mechanisms of miRNAs in the Development of Osteosarcoma

“…[90][91][92] The signaling pathway promotes proliferation, survival, and epithelial-mesenchymal transition (EMT) while suppressing apoptosis. 93 The carcinogenesis of miRNA-23b-3p in colon adenocarcinoma, 94 hepatocellular carcinoma, 95 and esophageal squamous cell carcinomas 96 has been confirmed. In osteosarcoma, miRNA-23b-3p can promote osteosarcoma by targeting VEPH1/ PI3K/AKT signaling pathway.…”

Lnc-PLA2G4A-4 facilitates the progression of hepatocellular carcinoma by inducing versican expression via sponging miR-23b-3p

“…Among them, miR-23b-3p attracted our attention, because it acts as both a tumor suppressor [ [35] , [36] , [37] ] and an oncogenic miRNA [ [38] , [39] , [40] ] in various types of carcinogenesis. There is accumulating evidence that miR-23b performed a variety of functions in various tumor progressions, which is involved in proliferation [ 41 ], apoptosis [ 42 ], metastasis [ 43 ], angiogenesis [ 44 ], chemoresistance [ 45 ] and glycolysis [ 45 ]. In addition, miR-23b was significantly down-regulated in LIHC dataset.…”

lncRNA TUSC7 regulates oxidative stress level by targeting miR-23b in colorectal cancer and thus inhibits cell proliferation, migration and invasion

“…In addition, miR-23b reduces the binding of PTEN to the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, thereby reducing the level of NLRP3dependent pyroptosis. When TUSC7 binds to miR-23b like a sponge, miR-23b is rendered inactive, which indirectly regulates oxidative stress levels in tumors [15][16][17][18].…”