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.

Bone Marrow Mesenchymal Stem Cells (BMSCs) with a Disintegrin and Metalloprotease 17 (ADAM17) Overexpression Increase Cervical Cancer Cell Proliferation and Migration Through Epidermal Growth Factor Receptor (EGFR)/Phosphatidylinositol 3-Kinase (PI3K)/Protein Kinase b (AKT) Signaling

2022 ◽  
Vol 12 (5) ◽  
pp. 1059-1064
Author(s):  
Li Gao ◽  
Shulan Lv ◽  
Yan Zhu
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Target Genes ◽  
Biological Activities ◽  
Akt Signaling ◽  
Control Group ◽  
Empty Vector ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

ADAM-17 is a membrane-bound protease and highly expressed in multiple tumors. BMSCs carrying target genes are delivered to damaged sites. This study aimed to investigate the mechanism underlying BMSCs with ADAM-17 in cervical cancer (CC). BMSCs were transfected with ADAM-17 mimics and co-cultured with CC cells followed by analysis of cell proliferation and migration by MTT assay and scratch assay, ADAM-17 and target genes (LAMB3, Robol) level by Western blot and RT-qPCR. As the effectiveness of ADAM-17 transfection was confirmed by its increased level, the presence of empty vector rarely affected ADAM-17 expression and biological activities of CC cells compared to control group (p > 0.05). BMSCs with ADAM-17 overexpression increased CC cell proliferation and enhanced scratch healing rate (p < 0.05), accompanied with upregulated LAMB3 and Robol. The difference in LAMB3 and Robol expression between empty vector group and control group did not reach a significance. In conclsuion, this study elucidates that BMSCs with ADAM-17 overexpression promotes CC cell progression through up-regulation of LAMB3 and Robol and activation EGFR/PI3K/Akt signaling, providing a novel BMSC-based targeted therapy.

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 TIPE Regulates DcR3 Expression and Function by Activating the PI3K/AKT Signaling Pathway in CRC

2021 ◽  
Vol 10 ◽  
Author(s):  
Mengya Zhong ◽  
Xingfeng Qiu ◽  
Yu Liu ◽  
Yan Yang ◽  
Lei Gu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Akt Signaling ◽  
Luciferase Reporter ◽  
Akt Signaling Pathway ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Hct116 Cells ◽  
Proliferation And Migration

Tumor necrosis factor-induced protein-8 (TIPE) is highly expressed in colorectal cancer (CRC). Decoy receptor 3 (DcR3) is a soluble secreted protein that can antagonize Fas ligand (FasL)-induced apoptosis and promote tumorigenesis. It remains unclear whether TIPE can regulate DcR3 expression. In this study, we examined this question by analyzing the relationship between these factors in CRC. Bioinformatics and tissue microarrays were used to determine the expression of TIPE and DcR3 and their correlation in CRC. The expression of TIPE and DcR3 in colon cancer cells was detected. Plasma samples were collected from CRC patients, and DcR3 secretion was measured. Then, dual-luciferase reporter gene analysis was performed to assess the interaction between TIPE and DcR3. We exogenously altered TIPE expression and analyzed its function and influence on DcR3 secretion. Lipopolysaccharide (LPS) was used to stimulate TIPE-overexpressing HCT116 cells, and alterations in signaling pathways were detected. Additionally, inhibitors were used to confirm molecular mechanisms. We found that TIPE and DcR3 were highly expressed in CRC patients and that their expression levels were positively correlated. DcR3 was highly expressed in the plasma of cancer patients. We confirmed that TIPE and DcR3 were highly expressed in HCT116 cells. TIPE overexpression enhanced the transcriptional activity of the DcR3 promoter. TIPE activated the PI3K/AKT signaling pathway to regulate the expression of DcR3, thereby promoting cell proliferation and migration and inhibiting apoptosis. In summary, TIPE and DcR3 are highly expressed in CRC, and both proteins are associated with poor prognosis. TIPE regulates DcR3 expression by activating the PI3K/AKT signaling pathway in CRC, thus promoting cell proliferation and migration and inhibiting apoptosis. These findings may have clinical significance and promise for applications in the treatment or prognostication of CRC.

scholarly journals miR-429 Suppresses Proliferation and Migration in Glioblastoma Cells and Induces Cell-cycle Arrest via Modulating Several Target Genes of ERBB Signaling Pathway

2021 ◽  
Author(s):  
Fatemeh Gheidari ◽  
Ehsan Arefian ◽  
Mahboubeh Kabiri ◽  
Ehsan Seyedjafari ◽  
Ladan Teimoori-Toolabi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Target Genes ◽  
Cycle Arrest ◽  
Cell Proliferation And Migration ◽  
Erbb Signaling ◽  
And Migration ◽  
Erbb Signaling Pathway ◽  
Proliferation And Migration

Abstract Glioblastoma is aggressive and lethal brain cancer, which is incurable by cancer standard treatments. miRNAs have great potential to be used for gene therapy due to their ability to modulate several target genes simultaneously. We found miR-429 is downregulated in glioblastoma and has several predicted target genes from the ERBB signaling pathway using bioinformatics tools. ERBB is the most over-activated genetic pathway in glioblastoma patients, which is responsible for augmented cell proliferation and migration in glioblastoma multiforme (GBM). Here we overexpressed miR-429 using lentiviral vectors in GBM U-251 cells and observed that the expression level of several oncogenes of the ERBB pathway, EGFR, PIK3CA, PIK3CB, KRAS, and MYC significantly decreased; as shown by real-time PCR and western blotting. Using the luciferase assay, we showed that miR-429 directly targets MYC, BCL2, and EGFR. In comparison to scrambled control, miR-429 had a significant inhibitory effect on cell proliferation and migration as deduced from MTT and scratch wound assays and induced cell-cycle arrest in flow cytometry. Altogether miR-429 seems to be an efficient suppressor of the ERBB genetic signaling pathway and a potential therapeutic for glioblastoma.

scholarly journals Inhibition of Carnitine Palmitoyl Transferase 1A-induced Fatty Acid Oxidation Suppresses Cell Progression in Gastric Cancer

2020 ◽  
Author(s):  
Liqiang Wang ◽  
Changfeng Li ◽  
Yumei Song ◽  
ZhenKun Yan
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
High Rate ◽  
Acid Oxidation ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: Gastric cancer (GC) has a high rate of metastasis which thereason leading to death. Carnitine palmitoyltransferase 1a (CPT1A) has been reported to play a critical obstacle to various types of cancer progression, which is an attractive focus in anti-cancer therapy. However, the underlying molecular mechanisms of CPT1A involved in GC have not been clarified unclear.Methods: To determine the expression of CPT1A in human GC tissues and cells and illustrate whether it is correlated with the clinical pathologic characteristics and prognosis in GC patients. Its roles and potential mechanisms in regulating tumor growth and invasion were evaluated by CPT1A knockdown/overexpression of GC cells in vitro.Results: Marked upregulation of CPT1A protein expression was observed in GC cells and tissues, which was associated with grade, pathological stage, lymph node metastasis and poor prognosis in patients with GC. CPT1A overexpression also promoted the proliferation, invasion, EMT process of GC cells. In addition, CPT1A upregulation activated GC cell FAO via increasing NADP+/NADPH ratio, whereasinhibiting of FAO abolished the effects of CPT1A on GC cell proliferation and migration.Conclusion: Our results examine that CPT1A-mediated FAO activation increases GC cell proliferation and migration, supporting that CPT1A is a useful prognostic biomarker and an attractive focus for GC.

scholarly journals Inhibition of carnitine palmitoyl transferase 1A-induced fatty acid oxidation suppresses cell progression in gastric cancer

2020 ◽  
Author(s):  
Liqiang Wang ◽  
Changfeng Li ◽  
Yumei Song ◽  
ZhenKun Yan
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Molecular Mechanisms ◽  
High Rate ◽  
Acid Oxidation ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: Gastric cancer (GC) has a high rate of metastasis which thereason leading to death. Carnitine palmitoyltransferase 1a (CPT1A) has been reported to play a critical obstacle to various types of cancer progression, which is an attractive focus in anti-cancer therapy. However, the underlying molecular mechanisms of CPT1A involved in GC have not been clarified unclear. Methods: To determine the expression of CPT1A in human GC tissues and cells and illustrate whether it is correlated with the clinical pathologic characteristics and prognosis in GC patients. Its roles and potential mechanisms in regulating tumor growth and invasion were evaluated by CPT1A knockdown/overexpression of GC cells in vitro . Results: Marked upregulation of CPT1A protein expression was observed in GC cells and tissues, which was associated with grade, pathological stage, lymph node metastasis and poor prognosis in patients with GC. CPT1A overexpression also promoted the proliferation, invasion, EMT process of GC cells. In addition, CPT1A upregulation activated GC cell FAO via increasing NADP + /NADPH ratio, whereas inhibiting of FAO abolished the effects of CPT1A on GC cell proliferation and migration. Conclusion: Our results examine that CPT1A-mediated FAO activation increases GC cell proliferation and migration, supporting that CPT1A is a useful prognostic biomarker and an attractive focus for GC. Keywords: CPT1A; gastric cancer; fatty acid oxidation; prognostic; progression

scholarly journals lncRNA DLEU2 promotes gastric cancer progression through ETS2 via targeting miR-30a-5p

2020 ◽  
Author(s):  
Shuyi Han ◽  
Yihui Xu ◽  
Min Wang ◽  
Jun Wang ◽  
Jing Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Tnm Stage ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Gastric cancer (GC) is the fourth common and the second lethal malignancy. Further understanding of the molecular mechanisms of underlying gastric carcinogenesis will enhance the diagnosis and treatment of GC. Methods The expression of lncRNA DLEU2 and ETS2 was analysed using GEPIA online analyze, qRT-PCR and immunohistochemistry. siRNAs targeting to lncRNA DLEU2 were designed to reduce the expression of lncRNA DLEU2. miR-30a-5p mimics were purchased to up-regulate the level of miR-30a-5p. The pcDNA3.1-ETS2 vector was synthesized to up-regulate the expression of ETS2. The biological function of GC cells was detected by CCK8, clone formation, transwell, wound healing, western blot, and flow cytometry assay. More in-depth mechanisms were studied. Results LncRNA DLEU2 was significantly up-regulated in GC tissues. The expression of lncRNA DLEU2 was significantly associated with pathological grading and TNM stage of GC patients. Furthermore, knockdown of lncRNA DLEU2 inhibited the proliferation, migration and invasion of AGS and MKN-45 cells, and induced cell apoptosis. We also found that miR-30a-5p could directly bind to the 3’ UTR region of ETS2. Moreover, lncRNA DLEU2 bound to miR-30a-5p through the same binding site, which facilitated the expression of ETS2. Knockdown of lncRNA DLEU2 reduced the protein level of intracellular ETS2 and inhibited the AKT phosphorylation. ETS2 was highly expressed in GC tissues. The expression of ETS2 was significantly associated with age, pathological grading and TNM stage. ETS2 overexpression promoted cell proliferation and migration of AGS and MKN-45 cells. Furthermore, ETS2 overexpression rescued cell proliferation and migration inhibition induced by lncRNA DLEU2 down-regulation and miR-30a-5p up-regulation in AGS and MKN-45 cells. These results showed that lncRNA DLEU2 may regulate GC cells process through miR-30a-5p/ETS2 axis. In addition, hypoxic microenvironment resulted in the accumulation and nucleation of HIF-1α in gastric cancer cells, and up-regulated the expression of DLEU2. Conclusions LncRNA DLEU2 was a potential molecular target for GC treatment.

scholarly journals LETR1 is a lymphatic endothelial-specific lncRNA governing cell proliferation and migration through KLF4 and SEMA3C

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Luca Ducoli ◽  
Saumya Agrawal ◽  
Eliane Sibler ◽  
Tsukasa Kouno ◽  
Carlotta Tacconi ◽  
...  
Keyword(s):  
Transcriptional Control ◽  
Target Genes ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Rna Seq ◽  
Epigenetic Factors ◽  
Ample Evidence ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

AbstractRecent studies have revealed the importance of long noncoding RNAs (lncRNAs) as tissue-specific regulators of gene expression. There is ample evidence that distinct types of vasculature undergo tight transcriptional control to preserve their structure, identity, and functions. We determine a comprehensive map of lineage-specific lncRNAs in human dermal lymphatic and blood vascular endothelial cells (LECs and BECs), combining RNA-Seq and CAGE-Seq. Subsequent antisense oligonucleotide-knockdown transcriptomic profiling of two LEC- and two BEC-specific lncRNAs identifies LETR1 as a critical gatekeeper of the global LEC transcriptome. Deep RNA-DNA, RNA-protein interaction studies, and phenotype rescue analyses reveal that LETR1 is a nuclear trans-acting lncRNA modulating, via key epigenetic factors, the expression of essential target genes, including KLF4 and SEMA3C, governing the growth and migratory ability of LECs. Together, our study provides several lines of evidence supporting the intriguing concept that every cell type expresses precise lncRNA signatures to control lineage-specific regulatory programs.

scholarly journals Rab1A promotes cell proliferation and migration by upregulating Gli1 in colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chaozhong Peng ◽  
Xiao Li ◽  
Zhixue Ye ◽  
Wenqing Wu
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Node Metastasis ◽  
Cell Proliferation And Migration ◽  
Promising Therapeutic Target ◽  
Promotive Effect ◽  
Guanosine Triphosphatase ◽  
And Migration ◽  
Proliferation And Migration

AbstractRab1A, as a highly conserved small guanosine triphosphatase (GTPase), plays contentious roles in different types of cancers. The role of Rab1A in colorectal cancer (CRC) has been described in previous studies, but the molecular mechanisms of Rab1A in CRC remain far from being addressed. In the present study, we found that Rab1A expression was significantly upregulated in CRC tissues and increased Rab1A expression correlated with tumor size, lymph node metastasis (LNM) and tumor-node-metastasis (TNM) stage of CRC patients. We also found that Rab1A exerts its promotive effect on CRC cell proliferation, migration and EMT progress. Further mechanistic experiments showed that glioma-associated oncogene-1 (Gli1), as a key transcriptional factor of the Hedgehog pathway, was implicated in Rab1A-mediated regulation of CRC cell proliferation and migration. In addition, Rab1A upregulated Gli1 expression through Smoothened homolog (SMO)-independent pathway. Finally, Rab1A activated mechanistic target of rapamycin (mTOR) signaling in CRC cells. Collectively, our results define Rab1A as a novel regulator of Gli1 to promote CRC cell proliferation and migration, and suggest that the Rab1A/mTOR/Gli1 axis may serve as a promising therapeutic target for the treatment of CRC.

Sign in / Sign up

Export Citation Format

Share Document