scholarly journals MEX3A contributes to development and progression of glioma through regulating cell proliferation and cell migration and targeting CCL2

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chao Yang ◽  
Haoqiang Zhan ◽  
Yiqing Zhao ◽  
Yasong Wu ◽  
Lisha Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Therapeutic Target ◽  
Malignant Tumors ◽  
Tumor Promoter ◽  
Mechanistic Study ◽  
High Morbidity ◽  
Loss Of Function

AbstractGlioma is one of the most commonly diagnosed intracranial malignant tumors with extremely high morbidity and mortality, whose treatment was seriously limited because of the unclear molecular mechanism. In this study, in order to identify a novel therapeutic target for glioma treatment, we explored the functions and mechanism of MEX3A in regulating glioma. The immunohistochemical staining of MEX3A in glioma and normal tissues revealed the upregulation of MEX3A and further indicated the relationship between high MEX3A expression and higher malignancy as well as poorer prognosis of glioma. In vitro loss-of-function and gain-of-function experiments comprehensively demonstrated that MEX3A may promote glioma development through regulating cell proliferation, cell apoptosis, cell cycle, and cell migration. In vivo experiments also suggested the inhibition of glioma growth by MEX3A knockdown. Moreover, our mechanistic study identifies CCL2 as a potential downstream target of MEX3A, which possesses similar regulatory effects on glioma development with MEX3A and could attenuate the promotion of glioma induced by MEX3A overexpression. Overall, MEX3A was identified as a potential tumor promoter in glioma development and therapeutic target in glioma treatment.

scholarly journals Notch3 inhibits cell proliferation and tumorigenesis and predicts better prognosis in breast cancer through transactivating PTEN

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Yong-Qu Zhang ◽  
Yuan-Ke Liang ◽  
Yang Wu ◽  
Min Chen ◽  
Wei-Ling Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Malignant Tumors ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Loss Of Function ◽  
Ki 67 ◽  
Cancer Subtypes

AbstractNotch receptors (Notch1–4) play critical roles in tumorigenesis and metastasis of malignant tumors, including breast cancer. Although abnormal Notch activation is related to various tumors, the importance of single receptors and their mechanism of activation in distinct breast cancer subtypes are still unclear. Previous studies by our group demonstrated that Notch3 may inhibit the emergence and progression of breast cancer. PTEN is a potent tumor suppressor, and its loss of function is sufficient to promote the occurrence and progression of tumors. Intriguingly, numerous studies have revealed that Notch1 is involved in the regulation of PTEN through its binding to CBF-1, a Notch transcription factor, and the PTEN promoter. In this study, we found that Notch3 and PTEN levels correlated with the luminal phenotype in breast cancer cell lines. Furthermore, we demonstrated that Notch3 transactivated PTEN by binding CSL-binding elements in the PTEN promoter and, at least in part, inhibiting the PTEN downstream AKT-mTOR pathway. Notably, Notch3 knockdown downregulated PTEN and promoted cell proliferation and tumorigenesis. In contrast, overexpression of the Notch3 intracellular domain upregulated PTEN and inhibited cell proliferation and tumorigenesis in vitro and in vivo. Moreover, inhibition or overexpression of PTEN partially reversed the promotion or inhibition of cell proliferation induced by Notch3 alterations. In general, Notch3 expression positively correlated with elevated expression of PTEN, ER, lower Ki-67 index, and incidence of involved node status and predicted better recurrence-free survival in breast cancer patients. Therefore, our findings demonstrate that Notch3 inhibits breast cancer proliferation and suppresses tumorigenesis by transactivating PTEN expression.

scholarly journals LncRNA RCAT1 promotes tumor progression and metastasis via miR-214-5p/E2F2 axis in renal cell carcinoma

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Renbo Guo ◽  
Benkui Zou ◽  
Yiran Liang ◽  
Jiasheng Bian ◽  
Jian Xu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Malignant Tumors ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Mortality And Morbidity

AbstractRenal cell carcinoma is the second malignant tumors in the urinary system with high mortality and morbidity. Increasing evidence suggests that long non-coding RNAs (lncRNAs) play critical roles in tumor development and progression. In the current study, based on the publicly available data obtained from GEO and TCGA database, we identified five prognosis-related lncRNAs with the ability to predict the prognosis of patients with renal cell carcinoma. Among them, the uncharacterized and upregulated lncRNA RCAT1 (renal cancer-associated transcript 1) was identified as the key lncRNA. Our data further revealed that the expression of lncRNA RCAT1 was significantly upregulated in renal cell carcinoma tissues and cells. Gain-of-function and loss-of-function studies showed that lncRNA RCAT1 promoted cell proliferation, migration, and invasion in vitro and in vivo. Furthermore, we verified that lncRNA RCAT1 could abundantly sponge miR-214-5p, which served as a tumor suppressor in renal cell carcinoma. Significantly, miR-214-5p overexpression could attenuate the promotion of cell proliferation and metastasis induced by lncRNA RCAT1. Moreover, we found that E2F2 was a direct target of miR-214-5p, and lncRNA RCAT1 could protect E2F2 from miR-214-5p-mediated degradation. Taken together, our findings suggested that lncRNA RCAT1 could enhance the malignant phenotype of renal cell carcinoma cells by modulating miR‐214‐5p/E2F2 axis, and lncRNA RCAT1 might be a novel prognostic biomarker and a potential therapeutic target for renal cell carcinoma.

scholarly journals CDK13 upregulation-induced formation of the positive feedback loop among circCDK13, miR-212-5p/miR-449a and E2F5 contributes to prostate carcinogenesis

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Jin-Chun Qi ◽  
Zhan Yang ◽  
Tao Lin ◽  
Long Ma ◽  
Ya-Xuan Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Transcriptional Activation ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Biological Effects ◽  
Therapeutic Benefit ◽  
Loss Of Function ◽  
Positive Feedback Loop

Abstract Background Both E2F transcription factor and cyclin-dependent kinases (CDKs), which increase or decrease E2F activity by phosphorylating E2F or its partner, are involved in the control of cell proliferation, and some circRNAs and miRNAs regulate the expression of E2F and CDKs. However, little is known about whether dysregulation among E2Fs, CDKs, circRNAs and miRNAs occurs in human PCa. Methods The expression levels of CDK13 in PCa tissues and different cell lines were determined by quantitative real-time PCR and Western blot analysis. In vitro and in vivo assays were preformed to explore the biological effects of CDK13 in PCa cells. Co-immunoprecipitation anlysis coupled with mass spectrometry was used to identify E2F5 interaction with CDK13. A CRISPR-Cas9 complex was used to activate endogenous CDK13 and circCDK13 expression. Furthermore, the mechanism of circCDK13 was investigated by using loss-of-function and gain-of-function assays in vitro and in vivo. Results Here we show that CDK13 is significantly upregulated in human PCa tissues. CDK13 depletion and overexpression in PCa cells decrease and increase, respectively, cell proliferation, and the pro-proliferation effect of CDK13 is strengthened by its interaction with E2F5. Mechanistically, transcriptional activation of endogenous CDK13, but not the forced expression of CDK13 by its expression vector, remarkably promotes E2F5 protein expression by facilitating circCDK13 formation. Further, the upregulation of E2F5 enhances CDK13 transcription and promotes circCDK13 biogenesis, which in turn sponges miR-212-5p/449a and thus relieves their repression of the E2F5 expression, subsequently leading to the upregulation of E2F5 expression and PCa cell proliferation. Conclusions These findings suggest that CDK13 upregulation-induced formation of the positive feedback loop among circCDK13, miR-212-5p/miR-449a and E2F5 is responsible for PCa development. Targeting this newly identified regulatory axis may provide therapeutic benefit against PCa progression and drug resistance.

scholarly journals DPP3/CDK1 contributes to the progression of colorectal cancer through regulating cell proliferation, cell apoptosis, and cell migration

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Yixin Tong ◽  
Yuan Huang ◽  
Yuchao Zhang ◽  
Xiangtai Zeng ◽  
Mei Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Apoptosis ◽  
Downstream Target ◽  
Normal Tissues ◽  
Physiological Processes ◽  
Mutual Regulation

AbstractAt present, colorectal cancer (CRC) has become a serious threat to human health in the world. Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent hydrolase that may be involved in several physiological processes. However, whether DPP3 affects the development and progression of CRC remains a mystery. This study is the first to demonstrate the role of DPP3 in CRC. Firstly, the results of immunohistochemistry analysis showed the upregulation of DPP3 in CRC tissues compared with normal tissues, which is statistically analyzed to be positively correlated with lymphatic metastasis, pathological stage, positive number of lymph nodes. Moreover, the high expression of DPP3 predicts poor prognosis in CRC patients. In addition, the results of cell dysfunction experiments clarified that the downregulation of DPP3 significantly inhibited cell proliferation, colony formation, cell migration, and promoted apoptosis in vitro. DPP3 depletion could induce cell apoptosis by upregulating the expression of BID, BIM, Caspase3, Caspase8, HSP60, p21, p27, p53, and SMAC. In addition, downregulation of DPP3 can reduce tumorigenicity of CRC cells in vivo. Furthermore, CDK1 is determined to be a downstream target of DPP3-mediated regulation of CRC by RNA-seq, qPCR, and WB. The interaction between DPP3 and CDK1 shows mutual regulation. Specifically, downregulation of DPP3 can accentuate the effects of CDK1 knockdown on the function of CRC cells. Overexpression of CDK1 alleviates the inhibitory effects of DPP3 knockdown in CRC cells. In summary, DPP3 has oncogene-like functions in the development and progression of CRC by targeting CDK1, which may be an effective molecular target for the prognosis and treatment of CRC.

scholarly journals DEPDC1B is a tumor promotor in development of bladder cancer through targeting SHC1

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Chin-Hui Lai ◽  
Kexin Xu ◽  
Jianhua Zhou ◽  
Mingrui Wang ◽  
Weiyu Zhang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Malignant Tumors ◽  
Tumor Grade ◽  
In Vivo Studies ◽  
Mechanistic Study ◽  
Tumor Promotor ◽  
Bladder Cancer Cells

AbstractBladder cancer is one of the most commonly diagnosed malignant tumors in the urinary system and causes a massive cancer-related death. DEPDC1B is a DEP domain-containing protein that has been found to be associated with a variety of human cancers. This study aimed to explore the role and mechanism of DEPDC1B in the development of bladder cancer. The analysis of clinical specimens revealed the upregulated expression of DEPDC1B in bladder cancer, which was positively related to tumor grade. In vitro and in vivo studies showed that DEPDC1B knockdown could inhibit the growth of bladder cancer cells or xenografts in mice. The suppression of bladder cancer by DEPDC1B was executed through inhibiting cell proliferation, cell migration, and promoting cell apoptosis. Moreover, a mechanistic study found that SHC1 may be an important route through which DEPDC1B regulates the development of bladder cancer. Knockdown of SHC1 in DEPDC1B-overexpressed cancer cells could abolish the promotion effects induced by DEPDC1B. In conclusion, DEPDC1B was identified as a key regulator in the development of bladder cancer, which may be used as a potential therapeutic target in the treatment of bladder cancer.

scholarly journals Clinical Utility of Ghrelin-O-Acyltransferase (GOAT) Enzyme as a Diagnostic Tool and Potential Therapeutic Target in Prostate Cancer

2019 ◽  
Vol 8 (12) ◽  
pp. 2056 ◽  
Author(s):  
Juan M. Jiménez-Vacas ◽  
Enrique Gómez-Gómez ◽  
Antonio J. Montero-Hidalgo ◽  
Vicente Herrero-Aguayo ◽  
Fernando L-López ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Therapeutic Target ◽  
Xenograft Model ◽  
Grey Zone ◽  
Pathophysiological Role ◽  
Expression Activity ◽  
Du145 Cells

Recent data suggested that plasma Ghrelin O-Acyl Transferase enzyme (GOAT) levels could represent a new diagnostic biomarker for prostate cancer (PCa). In this study, we aimed to explore the diagnostic and prognostic/aggressiveness capacity of GOAT in urine, as well as to interrogate its putative pathophysiological role in PCa. We analysed urine/plasma levels of GOAT in a cohort of 993 patients. In vitro (i.e., cell-proliferation) and in vivo (tumor-growth in a xenograft-model) approaches were performed in response to the modulation of GOAT expression/activity in PCa cells. Our results demonstrate that plasma and urine GOAT levels were significantly elevated in PCa patients compared to controls. Remarkably, GOAT significantly outperformed PSA in the diagnosis of PCa and significant PCa in patients with PSA levels ranging from 3 to 10 ng/mL (the so-called PSA grey-zone). Additionally, urine GOAT levels were associated to clinical (e.g., Gleason-score, PSA levels) and molecular (e.g., CDK2/CDK6/CDKN2A expression) aggressiveness parameters. Indeed, GOAT overexpression increased, while its silencing/blockade decreased cell-proliferation in PCa cells. Moreover, xenograft tumors derived from GOAT-overexpressing PCa (DU145) cells were significantly higher than those derived from the mock-overexpressing cells. Altogether, our results demonstrate that GOAT could be used as a diagnostic and aggressiveness marker in urine and a therapeutic target in PCa.

scholarly journals PHF14 Promotes Cell Proliferation and Migration through the AKT and ERK1/2 Pathways in Gastric Cancer Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Yuzu Zhao ◽  
Jiang He ◽  
Yongsen Li ◽  
Man Xu ◽  
Xingzhi Peng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Tumor Development ◽  
Tumor Promoter ◽  
Clinical Samples ◽  
Gastric Cancer Cells ◽  
Phosphorylated Akt

PHF14 is a new member belonging to PHD finger proteins. PHF14 is involved in multiple biologic processes including Dandy–Walker syndrome, mesenchyme growth, lung fibrosis, renal fibrosis, persistent pulmonary hypertension, and tumor development. This study aims to explore whether PHF14 plays an important role in gastric cancer. Here, PHF14 is indicated as a tumor promoter. The expression of PHF14 enhances no matter in clinical samples or in gastric cancer cells. High expression of PHF14 impairs survival of patients. Attenuation of PHF14 inhibits cell proliferation in gastric cancer cells. PHF14 downregulation inhibits the expression of cell cycle-related proteins, CDK6 and cyclin D1. Furthermore, silencing of PHF14 reduces the level of phosphorylated AKT as well as phosphorylated ERK1/2. Finally, downregulation of PHF14 in gastric cancer cells inhibits colony formation in vitro and tumorigenesis in vivo. These results indicate that PHF14 promotes tumor development in gastric cancer, so PHF14 thereby acts as a potential target for gastric cancer therapy.

The effect of pH on cell viability, cell migration, cell proliferation, wound closure, and wound reepithelialization: In vitro and in vivo study

2017 ◽  
Vol 25 (2) ◽  
pp. 260-269 ◽  
Author(s):  
Carla R. Kruse ◽  
Mansher Singh ◽  
Stefan Targosinski ◽  
Indranil Sinha ◽  
Jens A. Sørensen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Viability ◽  
Wound Closure ◽  
In Vivo Study ◽  
Effect Of Ph

scholarly journals Apigenin Protects the Brain against Ischemia/Reperfusion Injury via Caveolin-1/VEGF In Vitro and In Vivo

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Qiongyi Pang ◽  
Yun Zhao ◽  
Xiang Chen ◽  
Kaiyi Zhao ◽  
Qiongxiang Zhai ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Tube Formation ◽  
Caveolin 1 ◽  
The Brain

Apigenin is a natural flavonoid found in several dietary plant foods as vegetables and fruits. To investigate potential anti-ischemia/reperfusion injury properties of apigenin in vitro, cell proliferation assay, tube formation, cell migration, apoptosis, and autophagy were performed in human brain microvascular endothelial cells (HBMVECs) after oxygen-glucose deprivation/reoxygenation (OGD/R). The effect of apigenin was also explored in rats after middle cerebral artery occlusion/reperfusion (MCAO/R) via neurobehavioral scores, pathological examination, and measurement of markers involved in ischemia/reperfusion injury. Data in vitro indicated that apigenin could prompt cell proliferation, tube formation, and cell migration while inhibiting apoptosis and autophagy by affecting Caveolin-1/VEGF, Bcl-2, Caspase-3, Beclin-1, and mTOR expression. Results in vivo showed that apigenin significantly reduced neurobehavioral scores and volume of cerebral infarction while prompting vascular endothelial cell proliferation by upregulating VEGFR2/CD34 double-labeling endothelial progenitor cell (EPC) number and affecting Caveolin-1, VEGF, and eNOS expression in brain tissue of MCAO/R rats. All the data suggested that apigenin may be protective for the brain against ischemia/reperfusion injury by alleviating apoptosis and autophagy, promoting cell proliferation in HBMVECs of OGD/R, and attenuating brain damage and improved neurological function in rats of MCAO/R through the Caveolin-1/VEGF pathway.

Biological and Therapeutic Potential of Mir-155, 585 and Let-7f in Myeloma in Vitro and In Vivo.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 833-833
Author(s):  
Sophia Adamia ◽  
Mariateresa Fulciniti ◽  
Herve Avet-Loiseau ◽  
Samir B Amin ◽  
Parantu Shah ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Tumor Size ◽  
Therapeutic Potential ◽  
Mrna Translation ◽  
Biological Role ◽  
Loss Of Function

Abstract Abstract 833 A growing body of evidence suggests that the genome of a many organisms, particularly mammals is controlled not only by transcription factors but also by post-transcriptional programs that are modulated by the family of small RNA molecules including microRNAs (miRs). miRs can block mRNA translation and affect mRNA stability. We have evaluated profiles of 384 human miRs in CD138+ cells from 79 patients with multiple myeloma (MM), 11 MM cell lines and 9 healthy donors (HD) using qRT-PCR based microRNA array. This analysis has identified a MM specific miRNA signature that significantly correlates with OS (p=0.05) and EFS (p=0.017) of patients. Based on this signature one group of patients clustered with HD suggesting indolent disease while other with cell lines indicating aggressive disease. We identified significant modulation of expression of 61 microRNAs in MM cells compared to normal plasma cells. Specific miRs with established oncogenic and tumor suppressor functions such as miR-155, miR-585 and Let7-f were significantly dysregulated in MM (p<0.001). Modulation of miRs-155, -585 and Let7 were observed most frequently in the group of patients with poor OS and EFS suggesting their crucial role in MM. However biological role of these miRs have not yet been defined. To further evaluate biological function of these most recurrent miRs in MM, we evaluated role of miR-155, let-7f and mir-585 in MM cell lines by gain- and loss- of function experiments. We used locked nucleic acid (LNA) anti-miR probes for loss of function and pre-miR-155 for gain of function studies using them alone or in combination. Although manipulation of all 3 miRs induced 20-25% change in MM cell proliferation and/or induction of apoptosis, combination of anti-miR-let7f with pre-miR-155, and anti-miR-585 in combination with miR-155 had dramatic effects on MM cell proliferation and over 60% cells undergoing apoptosis. To evaluate the targets of these miRs, we have determined effects of these anti-miRs and pre-miR on global gene and miR expression profile in MM alone and in combinations. This analysis identified modulation of cluster of miRs as well as genes critical for cell growth and survival. Next, we have tested efficacy of these miRs in vivo in murine Xenograft model to evaluate their therapeutic potential. Tumor-bearing mice were treated intraperitoneal for four consecutively days with the LNA anti-miR-585 and Let-7 and pre-miR-155 probes and respective controls alone and in combination. We observed that the single LNA anti-miR-585 and let 7 and pre miR-155 treatment reduced tumor size by 36%, 31% and 155% in animal 7 days after treatment. However, significant tumor size reductions were achieved when animals were treated with combinations; anti-miR-Let 7f plus pre-miR-155 (58 %); LNA anti-miR-Let 7f plus LNA anti-miR-585 (56 %); LNA-anti-miR-585 plus pre-miR-155 (74 %).We did not observe any significant systemic toxicity in the animals. In conclusion our results suggest significant biological role for miR-585, let 7f and miR-155 in myeloma, both in vitro and in vivo; it highlights for the first time a concerted activity of combination of miRs and holds a great promise for developing novel therapeutic approach for myeloma. Disclosures: No relevant conflicts of interest to declare.

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