MicroRNA‑9‑5p functions as a tumor suppressor in papillary thyroid cancer via targeting BRAF

Abstract

MicroRNAs (miRNAs/miRs) are widely studied as key regulators of gene expression and are involved in various diseases by affecting the miRNA-mediated regulatory function. BRAF is an important oncogene in the regulation of cell proliferation and apoptosis. In the present study, reverse transcription-quantitative polymerase chain reaction was used to determine the expression levels of miR-9-5p and BRAF mRNA in patients with papillary thyroid cancer (PTC). Western blotting was used to detect BRAF protein level. A luciferase assay was used to verify the miR-9-5p target site in BRAF. Cell Counting Kit-8 and flow cytometry were used to assess cell proliferation, and apoptosis, respectively. In the present study, it was demonstrated that miR-9-5p is downregulated in malignant PTC. Using bioinformatics analysis, miR-9-5p was predicted to target the human BRAF 3'-untranslated region (3'-UTR). A dual-luciferase assay demonstrated that miR-9-5p downregulated BRAF expression by directly targeting its 3'-UTR. Mutations in the 3'-UTR of BRAF completely abolished its interaction with miR-9-5p. Expression of exogenous miRNA that mimics miR-9-5p miRNA decreased BRAF protein and mRNA levels, while suppression of endogenous miR-9-5p resulted in an increase in BRAF protein, and mRNA levels. Furthermore, regulation of miR-9-5p was observed to suppress the viability of PTC cells by inducing apoptosis. Consistently, downregulation of miR-9-5p promoted proliferation of PTC cells by inhibiting the apoptosis of cells. In conclusion, the present study demonstrated that miR-9-5p may perform an important role in PTC prognosis and therapy.

Protective role of microRNA-9-5p in oxygen glucose deprivation/reperfusion-induced injury in liver sinusoidal endothelial cell

“…Moreover, Tanoi et al showed that inhibition of Bax in LSECs reduces apoptosis in both LSECs and hepatocytes [39]. In contrast to our nding, recent studies show that miR-9-5p may induce apoptosis in papillary thyroid cancer and oral squamous cell carcinoma [14,15]. This may be attributable to cell type, pathological conditions, and more importantly, targeting factors.…”

“…MiR-9-5p have been extensively studied in malignant diseases, such as oral squamous cell carcinoma, nasopharyngeal carcinoma, papillary thyroid cancer, and prostate cancer, etc. [13][14][15][16][17] Depending on the speci c cell type and pathological conditions, miR-9-5p may exert either pro-apoptotic or anti-apoptotic functions. We previously have shown that miR-9-5p protected human umbilical vascular endothelial cells (HUVEC) against apoptosis and excessive in ammatory response via downregulation of CXC chemokine receptor-4 (CXCR4) [18].…”

The miR-26b-5p/KPNA2 Axis Is an Important Regulator of Burkitt Lymphoma Cell Growth

“…An oncogenic role was shown for miR-106b-5p in non-small cell lung cancer, renal cell carcinoma, and glioma tumor [27,34,35]. Interestingly, miR-9-5p was shown to have both tumor suppressor and oncogenic properties in different cancers [36,37]. In HL, it was shown that miR-9-5p impaired tumor outgrowth in a xenograft model of HL [38].…”

High Glucose Concentrations Negatively Regulate the IGF1R/Src/ERK Axis through the MicroRNA-9 in Colorectal Cancer

“…The direct targets of microRNA are molecules at transcriptional level; for example, miR-9 directly downregulates TM4SF1 to suppress cell migration and invasion in CRC [60]. In addition, a previous study demonstrated that expression of exogenous miR-9-5p decreased BRAF protein and mRNA levels, and BRAF is a direct target of miR-9-5p in the tumorigenesis of papillary thyroid cancer (PTC) [61]. RAF is crucial in IGF1R/SHC/RAF/MAPK signaling pathway [24].…”