MicroRNA‐193a‐5p exerts a tumor suppressor role in glioblastoma via modulating NOVA1

Abstract

Background and Objectives Glioblastoma (GBM) is the most common and lethal of intracranial tumors, which is characterized by extensive proliferation and the diffused invasion of tumor cells. MicroRNA‐193a‐5p (miR‐193a‐5p) have been demonstrated previously as a functional suppressor in the development and progression of various cancers. The current study aimed to investigate whether miR‐193a‐5p influences cell proliferation and migration through the mitogen‐activated protein kinase/extracellular signal‐regulated kinase signaling pathway by targeting neuro‐oncological ventral antigen 1 (NOVA1) in glioblastoma. Materials and Methods The miR‐193a‐5p expression was detected by quantitative real‐time polymerase chain reaction assay in GBM tissues and cell lines. Cell Counting Kit‐8 assay, colony formation analysis, wound‐healing, and transwell invasion assays were performed to evaluate cell proliferation, colony formation, migration, and invasion, respectively. Western blot analysis and luciferase reporter gene assay were performed to verify the downstream target gene of miR‐193a‐5p. Results The expression of miR‐193a‐5p was significantly downregulated in GBM tissues and cell lines. Kaplan‐Meier analysis showed that patients with low miR‐193a‐5p expression had a shorter disease‐free survival (P < 0.05). Functionally, miR‐193a‐5p overexpression dramatically suppressed the proliferation, colony formation, migration, and invasion in glioma cells. Bioinformatics prediction and a luciferase assay confirmed that NOVA1 was a direct functional target of miR‐193a‐5p. Moreover, ectopic expression of NOVA1 could partially reverse the inhibitory effects of miR‐193a‐5p on glioma cell proliferation, colony formation, migration, and invasion. NOVA1 overexpression abrogated the inhibitory effect of miR‐193a‐5p on the PTEN/PI3k/AKT pathway. Conclusion Taken together, our findings suggested that miR‐193a‐5p functions as a tumor suppressor in glioma cells by directly targeting NOVA1.

CircCSPP1 Functions as a ceRNA to Promote Colorectal Carcinoma Cell EMT and Liver Metastasis by Upregulating COL1A1

“…miR-193a-5p has been studied in several tumors and plays a vital role in the post-transcriptional regulation of signaling pathway proteins (31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41). For example, miR-193a-5p suppressed tumor cell metastasis and epithelial-to-mesenchymal transition by targeting WT1-E-cadherin in non-small-cell lung cancers (41).…”

<p>MicroRNA-559 plays an inhibitory role in the malignant progression of glioblastoma cells by directly targeting metadherin</p>

“…25 Expression of several miRNAs has been reported to be dysregulated in GBM and to play a significant part in GBM formation and progression. [26][27][28] MiRNAs may perform tumorsuppressive or tumor-promoting functions in GBM through regulation of the expression of their target genes. 29 Hence, elucidation of the functions of cancerassociated miRNAs in GBM may facilitate the identification of promising therapeutic targets in GBM.…”

MicroRNA‑193a‑5p exerts a tumor suppressive role in epithelial ovarian cancer by modulating RBBP6

“…A previous study also reported an improvement to membranous nephropathy following miR-193a inhibition, which affected podocytosis by targeting WT1 transcription factor (WT1) (28). Jin et al (29) demonstrated that miR-193a-5p exerted a tumor-suppressive role in glioblastoma via modulating NOVA alternative splicing regulator 1. In addition, Shirafkan et al (18) identified that miR-193a-5p inhibited human HT-29 colon cancer cell migration by suppressing the metastatic pathway.…”