scholarly journals miR-6743-5p, as a direct upstream regulator of GRIM-19, enhances proliferation and suppresses apoptosis in glioma cells

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Fang Cao ◽  
Qiang Zhang ◽  
Wei Chen ◽  
Feng Zheng ◽  
Qishan Ran ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
Glioma Cells ◽  
Significant Inhibition ◽  
Signal Transducer ◽  
Upstream Regulator ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
And Migration ◽  
Transcription 3

Gene associated with retinoid-interferon-induced mortality-19 (GRIM-19) has been recognized as a tumor suppressor protein, which regulates cell growth, apoptosis, and migration by signal transducer and activator of transcription 3 (STAT3) signaling pathway and non-STAT3 pathway in glioma cells. Here, we investigated the molecular mechanisms that regulated GRIM-19 expression in glioma cells. By the TargetScan algorithm, four miRNAs, hsa-miR-17-3p, hsa-miR-423-5p, hsa-miR-3184-5p, and hsa-miR-6743-5p, were identified with the potential to bind with 3′-UTR of GRIM-19. Further miRNA inhibitor transfection and luciferase assays revealed that miR-6743-5p was able to directly target the 3′-UTR of GRIM-19. Additionally, miR-6743-5p expression was inversely related with GRIM-19 expression in glioma specimens and cell lines. Moreover, the inhibition of miR-6743-5p caused a significant inhibition of cell proliferation and a marked promotion of cell apoptosis in glioma cells, and this phenotype was rescued by GRIM-19 knockdown. Finally, the inhibition of miR-6743-5p expression suppressed the phosphorylation of STAT3, and the mRNA expression of CyclinD1 and Bcl-2, two target genes of STAT3, while miR-6743-5p mimic had the inversed effects. Treatment with STAT3 inhibitor AG490 partially rescued the proliferation-promoting and anti-apoptosis effects of miR-6743-5p overexpression or GRIM-19 knockdown. Collectively, miR-6743-5p may act as an oncomiRNA in glioma by targetting GRIM-19 and STAT3.

scholarly journals Targeting STAT3 Signaling Pathway in Colorectal Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1016
Author(s):  
Antonios N. Gargalionis ◽  
Kostas A. Papavassiliou ◽  
Athanasios G. Papavassiliou
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cell Proliferation ◽  
Signal Transducer ◽  
Innate And Adaptive Immunity ◽  
Invasion And Migration ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Promising Therapeutic Target ◽  
And Migration ◽  
Transcription 3

Signal transducer and activator of transcription 3 (STAT3) is a critical transcription factor that has been firmly associated with colorectal cancer (CRC) initiation and development. STAT3 mediates key inflammatory mechanisms in colitis-associated cancer, becomes excessively activated in CRC, and enhances cancer cell proliferation, tumor growth, angiogenesis, invasion, and migration. STAT3 hyperactivation in malignant cells, surrounding immune cells and cancer-associated fibroblasts, mediates inhibition of the innate and adaptive immunity of the tumor microenvironment, and, therefore, tumor evasion from the immune system. These features highlight STAT3 as a promising therapeutic target; however, the mechanisms underlying these features have not been fully elucidated yet and STAT3 inhibitors have not reached the clinic in everyday practice. In the present article, we review the STAT3 signaling network in CRC and highlight the current notion for the design of STAT3-focused treatment approaches. We also discuss recent breakthroughs in combination immunotherapy regimens containing STAT3 inhibitors, therefore providing a new perception for the clinical application of STAT3 in CRC.

MiR-3666 serves as a tumor suppressor in ovarian carcinoma by down-regulating AK4 via targeting STAT3

2020 ◽  
pp. 1-9
Author(s):  
Huiping Tan ◽  
Chunlin Wu ◽  
Bo Huang ◽  
Lei Jin ◽  
Xiangbing Jiang
Keyword(s):  
Ovarian Carcinoma ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Biological Activities ◽  
Signal Transducer ◽  
Cell Proliferation And Migration ◽  
Induce Cell Apoptosis ◽  
And Migration ◽  
Transcription 3 ◽  
Proliferation And Migration

As a result of metastasis and high recurrence, ovarian carcinoma (OC) is one of the most frequent gynecological carcinomas affecting women up to now. In spite of advances in OC treatments, the molecular mechanisms underlying OC progression are still needed to be deeply understood. MicroRNAs (miRNAs) with aberrant expressions are widely known to regulate target genes so as to mediate diverse biological activities of tumor cells. In the present study, we inspected the expression profile and latent mechanism of miR-3666 in OC. First of all, our research revealed the down-regulated miR-3666 in OC cells. Furthermore, miR-3666 up-regulation could repress cell proliferation and migration as well as induce cell apoptosis in OC. In addition, we unmasked that miR-3666 targeted STAT3 (signal transducer and activator of transcription 3) and further down-regulated STAT3 expression. Moreover, adenylate kinase 4 (AK4) was transcriptionally enhanced by STAT3, and then miR-3666 restrained AK4 expression by mediating STAT3. In the end, rescue experiments depicted that miR-3666 suppressed the development of OC via STAT3-mediated AK4. We uncovered that miR-3666 inhibited the tumorigenesis and even development of OC via suppressing STAT3/AK4 axis, offering a novel biomarker and therapeutic target for OC.

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