scholarly journals MiR-5195-3p Functions as a Tumor Suppressor in Prostate Cancer via Targeting CCNL1

2020 ◽  
Author(s):  
Xing Zeng ◽  
Zhiquan Hu ◽  
Yuanqing Shen ◽  
Xian Wei ◽  
Jiahua Gan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Tumor Suppressor ◽  
Clinical Significance ◽  
Cox Regression ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Cell Cycle Distribution ◽  
Survival Prognosis

Abstract BackgroundAccumulating evidence indicates miR-5195-3p exerts tumor suppressive role in several tumors. However, there is limited research on the clinical significance and biological function of miR-5195-3p in prostate cancer (PCa).MethodsExpression levels of miR-5195-3p and Cyclin L1 (CCNL1) were determined using quantitative real-time PCR. The clinical significance of miR-5195-3p in PCa patients was evaluated using Kaplan-Meier survival analysis and Cox regression models. Cell proliferation and cell cycle distribution were measured by CCK-8 assay and flow cytometry, respectively. The association between miR-5195-3p and CCNL1 was analyzed by luciferase reporter assay.ResultsMiR-5195-3p expression levels were significantly downregulated in 69 paired PCa tissues compared with matched adjacent normal tissues. The decreased miR-5195-3p expression was associated with Gleason score and TNM stage, as well as worse survival prognosis. The in vitro experiments showed that miR-5195-3p overexpression suppressed the proliferation and cell cycle G1/S transition in PC-3 and DU145 cells. Elevated miR-5195-3p abundance was also demonstrated to impair tumor formation in vivo using PC-3 xenografts. Mechanistically, Cyclin L1 (CCNL1) was a direct target of miR-5195-3p in PCa cells, which was inversely correlated with miR-5195-3p in PCa tissues. Importantly, CCNL1 knockdown imitated, while overexpression reversed the effects of miR-5195-3p overexpression on PCa cell proliferation and cell cycle G1/S transition.ConclusionsOur data suggests that miR-5195-3p functions as a tumor suppressor via downregulating G1/S related CCNL1 expression in PCa.

scholarly journals MiR-20a-5p functions as a potent tumor suppressor by targeting PPP6C in acute myeloid leukemia

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0256995
Author(s):  
Fengchang Bao ◽  
Lei Zhang ◽  
Xiaohang Pei ◽  
Cheng Lian ◽  
Yanhui Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Acute Myeloid Leukemia ◽  
Tumor Suppressor ◽  
Myeloid Leukemia ◽  
Tumor Xenograft ◽  
Luciferase Reporter ◽  
Survival Prognosis ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is as a highly aggressive and heterogeneous hematological malignancy. MiR-20a-5p has been reported to function as an oncogene or tumor suppressor in several tumors, but the clinical significance and regulatory mechanisms of miR-20a-5p in AML cells have not been fully understood. In this study, we found miR-20a-5p was significantly decreased in bone marrow from AML patients, compared with that in healthy controls. Moreover, decreased miR-20a-5p expression was correlated with risk status and poor survival prognosis in AML patients. Overexpression of miR-20a-5p suppressed cell proliferation, induced cell cycle G0/G1 phase arrest and apoptosis in two AML cell lines (THP-1 and U937) using CCK-8 assay and flow cytometry analysis. Moreover, miR-20a-5p overexpression attenuated tumor growth in vivo by performing tumor xenograft experiments. Luciferase reporter assay and western blot demonstrated that protein phosphatase 6 catalytic subunit (PPP6C) as a target gene of miR-20a-5p was negatively regulated by miR-20a-5p in AML cells. Furthermore, PPP6C knockdown imitated, while overexpression reversed the effects of miR-20a-5p overexpression on AML cell proliferation, cell cycle G1/S transition and apoptosis. Taken together, our findings demonstrate that miR-20a-5p/PPP6C represent a new therapeutic target for AML and a potential diagnostic marker for AML therapy.

scholarly journals Oncogenes - the basics

2018 ◽  
Vol 3 (4) ◽  
pp. 35-37
Author(s):  
Arnab Ghosh ◽  
Diasma Ghartimagar ◽  
Sushma Thapa
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Repair ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Normal Cell ◽  
Tumor Formation ◽  
Precursor Cell ◽  
Single Precursor ◽  
Normal Cell Cycle

Normal cell cycle and cell proliferation are regulated by several genes which can be broadly classified into 4 groups viz, proto-oncogenes, tumor suppressor genes, genes regulating apoptosis and genes involved in DNA repair. These genes may be defective due to different factors. The defective genes may lead to production of abnormal proteins which may lead to disruption of the normal cell cycle and proliferation. A single precursor cell with defective gene proliferates surpassing the normal physiologic regulatory process and leads to tumor formation, so, traditionally,it is said that “tumors are clonal”.

CD147 Promote Proliferation in Prostate Cancer Cell

2014 ◽  
Vol 912-914 ◽  
pp. 1915-1918
Author(s):  
Qing Fang ◽  
Fang Fang ◽  
Yu Lian Liu ◽  
Wen Ping Li ◽  
Li Guo Wang
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Prostate Cancer Cell ◽  
Cell Cycle Distribution ◽  
Cell Cycle Protein ◽  
Phase Arrest ◽  
Cd147 Expression ◽  
Potential Therapeutic Application

CD147 is expressed on the cell surface of most tumor cells, which results in cancer cells proliferation, invasion, metastasis and angiogenes. Our previous study indicated that CD147 could promote invasion andmetastasis of prostate cancer. However the role of CD147 on cell proliferation has not to be explored inprostate cancer. In this study, the effects of CD147 on cell proliferation of hormone-independent prostatecancer (LNCaP-AI) was investigated. In the present study, cell cycle distribution was investigated by flowcytometry and cell cycle protein were analysis by wester blot. The results demonstrated that knock-donwn CD147 expression induced G0/G1 phase arrest, and expression of cyclin D1 has potential suppressed with western blot analysis. The results suggest that CD147 could inhibit cell prolifearion and as potential therapeutic application in treatment of proste cancer.

scholarly journals LncRNA CRNDE acts as a ceRNA and regulates AML cell proliferation and apoptosis via miR136-5p/MCM5 axis

2020 ◽  
Author(s):  
Chen Liu ◽  
Liang Zhong ◽  
Chenlan Shen ◽  
Xuan Chu ◽  
Xu Luo ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Noncoding Rna ◽  
Colorectal Neoplasia ◽  
Luciferase Reporter ◽  
Cell Cycle Distribution ◽  
Risc Complex ◽  
Proliferation And Apoptosis ◽  
Rna Immunoprecipitation ◽  
Cell Processes

Abstract Background Increasing evidence demonstrated that long noncoding RNAs (lncRNAs) act as important factors in the regulation of cell processes and tumorigenesis. The long-noncoding RNA colorectal neoplasia differentially expressed (CRNDE) gene has been found to be related to several types of cancer. Although CRNDE is highly expressed in AML, its mechanism of action in acute myeloid leukemia (AML) is unknown. Methods The expression levels of CRNDE and miR-136-5p mRNAs were measured by quantitative real-time PCR. The effects of CRNDE knockdown on cell proliferation was assessed by the CCK8 assay, while apoptosis and cell cycle distribution were analyzed by flow cytometry. The expression of proteins related to cell cycle, cell apoptosis and MCM5 were analyzed by Western blotting. The luciferase reporter assay was used to confirm the interaction between CRNDE and miR-136-5p and between MCM5 and miR-136-5p in AML. The RNA immunoprecipitation assay was used to verify whether CRNDE exists in the miRNA mediated RISC complex. Results In this study, we used GEPIA database to confirm that CRNDE expression was significantly upregulated in AML samples. The silencing of CRNDE inhibited AML cells’ proliferation ability, increased AML cells’ apoptotic rate and arrested AML cells at the G1 phase of the cell cycle. Mechanistically, CRNDE served as a competing endogenous RNA (ceRNA) for miR-136-5p and upregulated MCM5 expression by sponging miR-136-5p. In addition, rescue assays revealed that the effects of CRNDE knockdown could be reversed by miR-136-5p inhibitors in AML cells. Conclusion Our results demonstrate that the CRNDE-miR-136-5p-MCM5 axis modulates AML progression and provide a new regulatory network of CRNDE in AML.

scholarly journals PSMC2 Regulates Cell Cycle Progression Through the p21/Cyclin D1 Pathway and Predicts a Poor Prognosis in Human Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Yiwei Liu ◽  
Hairong Chen ◽  
Xiangcheng Li ◽  
Feng Zhang ◽  
Lianbao Kong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cyclin D1 ◽  
Cell Cycle Progression ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Luciferase Reporter ◽  
Cycle Progression ◽  
Cox Regression Analysis

Proteasome 26S subunit ATPase 2 (PSMC2) plays a pathogenic role in various cancers. However, its function and molecular mechanism in hepatocellular carcinoma (HCC) remain unknown. In this study, tissue microarray (TMA) analysis showed that PSMC2 is highly expressed in HCC tumors and correlates with poor overall and disease-free survival in HCC patients. Multivariate Cox regression analysis revealed that PSMC2 is an independent prognostic factor for HCC patients. Furthermore, our results showed that PSMC2 knockdown inhibited cell proliferation and suppressed tumorigenesis in vivo. Knockdown of PSMC2 increased the expression of p21 and therefore decreased the expression of cyclin D1. Dual-luciferase reporter assays indicated that depletion of PSMC2 significantly enhanced the promoter activity of p21. Importantly, PSMC2 knockdown-induced phenotypes were also rescued by downregulation of P21. Taken together, our data suggest that PSMC2 promotes HCC cell proliferation and cell cycle progression through the p21/cyclin D1 signaling pathway and could be a promising diagnostic and therapeutic target for HCC patients.

scholarly journals Metformin exerts anti-AR-negative prostate cancer activity via AMPK/autophagy signaling pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chunyang Chen ◽  
He Wang ◽  
Xinyu Geng ◽  
Dongze Zhang ◽  
Zhengyu Zhu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Lines ◽  
Animal Experiments ◽  
Scratch Test ◽  
Tumor Formation ◽  
Cell Cycle Distribution ◽  
Ki 67 ◽  
Formation Experiment

Abstract Background Encouraged by the goal of developing an effective treatment strategy for prostate cancer, this study explored the mechanism involved in metformin-mediated inhibition of AR-negative prostate cancer. Methods Cell behaviors of DU145 and PC3 cells were determined by CCK8 test, colony formation experiment and scratch test. Flow cytometry was used to detect cell cycle distribution. Cell autophagy was induced with metformin, and an autophagy inhibitor, 3-MA, was used to assess the level of autophagy. Detection of LC3B by immunofluorescence was conducted to determine autophagy level. Cell proliferation, autophagy and cell cycle were examined by performing Western blot. DU145 and PC3 cell lines were transfected with AMPK siRNA targeting AMPK-α1 and AMPK-α2. Tumor formation experiment was carried out to evaluate the anti-prostate cancer effect of metformin in vivo. Results The inhibitory effect of metformin on the proliferation of prostate cancer cell lines was confirmed in this study, and the mechanism of such an effect was related to autophagy and the block of cell cycle at G0/G1 phase. Metformin also induced the activation of AMPK, markedly promoted expression of LC3II, and down-regulated the expression of p62/SQSTM1. Animal experiments showed that the tumor volume of metformin group was smaller, meanwhile, the levels of p-AMPK (Thr172) and LC3B were up-regulated and the Ki-67 level was down-regulated, without abnormalities in biochemical indicators. Conclusion This study found that autophagy induction might be the mechanism through which metformin suppressed the growth of AR-negative prostate cancer. Moreover, the activation of AMPK/autophagy pathway might be a therapeutically effective for treating AR-negative prostate cancer in the future.

scholarly journals Inhibitory role of circRNA_100395 in the proliferation and metastasis of prostate cancer cells

2021 ◽  
Vol 49 (2) ◽  
pp. 030006052199221
Author(s):  
Haitian He ◽  
Jianhua Li ◽  
Mayao Luo ◽  
Qiang Wei
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Counting ◽  
Cell Cycle Distribution ◽  
Prostate Cancer Cells ◽  
Mesenchymal Transition ◽  
Endogenous Expression ◽  
Proliferation And Metastasis

Objective Circular RNAs (circRNAs) are non-coding RNAs with high cancer-specific expression and the potential for regulating tumorigenesis. CircRNA_100395 is expressed at low levels in many cancers and is involved in the regulation of tumor cell proliferation and metastasis. However, its expression and function in prostate cancer remain unclear. Methods Endogenous expression levels of circRNA_100395 and microRNA-1228 (miR-1228) in prostate cancer tissue samples and cell lines were detected by quantitative reverse transcription-polymerase chain reaction. Cell proliferation, invasion, and migration, cell cycle distribution, and epithelial–mesenchymal transition (EMT) were analyzed in circRNA_100395-overexpressing prostate cancer cells by Cell Counting Kit-8, flow cytometry, Transwell assay, and western blotting, respectively. Results CircRNA_100395 expression was downregulated in cancerous prostate tissues relative to adjacent normal tissues. CircRNA_100395 expression was negatively correlated with tumor size, Gleason score, tumor stage, and lymph node metastasis. Moreover, circRNA_100395 overexpression inhibited cell proliferation, altered cell cycle distribution, reduced cell migration and invasion abilities, and suppressed EMT in prostate cancer cells. Moreover, miR-1228 was a direct downstream target of circRNA_100395, and the anti-tumor ability of circRNA_100395 was significantly reversed by miR-1228. Conclusion This study identified circRNA_100395 as an anti-tumor circRNA and a potential therapeutic target for prostate cancer.

scholarly journals Silencing LncRNA SCAMP1 Inhibits Cell Proliferation in Hepatocellular Carcinoma via Activation of p53 Signaling Pathway

2020 ◽  
Author(s):  
Xiaochen Ma ◽  
Xiangyang Sun ◽  
Caixia Li ◽  
Kai Zhang ◽  
Yang Xie
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Clinical Significance ◽  
Noncoding Rna ◽  
Cell Cycle Distribution ◽  
Survival Prognosis ◽  
Large Tumor ◽  
Tissue Samples ◽  
Expression Levels ◽  
P53 Signaling

Abstract Background: Long noncoding RNA secretory carrier membrane protein 1 (SCAMP1) has been recently reported to be an oncogene in several cancers, including glioma and ovarian cancer. However, its clinical significance and functional role in hepatocellular carcinoma (HCC) remain unknown.Methods: The expression of SCAMP1 was determined in tissue samples and cell lines using quantitative reverse transcription PCR. The clinical significance of SCAMP1 in HCC was evaluated using chi-squared test, Kaplan-Meier survival, as well as univariate and multivariate analysis. Cell proliferation, cell cycle distribution and apoptosis were evaluated using CCK-8 assay, colony formation assay, Flow cytometry analysis. Related protein expression levels were measured by western blot analysis.Results: We found SCAMP1 expression levels were remarkably up-regulated in HCC tissues compared with that in matched adjacent tissues. Increased SCAMP1 expression was significantly correlated with large tumor size, advanced TNM stage and poor survival prognosis in HCC. Knockdown of SCAMP1 significantly inhibited cell proliferation, induced G0/G1 phase arrest and apoptosis in HepG2 and SNU-182 cells. More importantly, knockdown of SCAMP1 downregulated the expression levels of CDK4, Cyclin D1 and Bcl-2, while upregulated the expression levels of p21, p53 and Bax.Conclusions: In summary, our study clarified the oncogenic role of SCAMP1 in HCC, and provided a potential therapeutic target for HCC treatment.

scholarly journals LncRNA CRNDE Acts as a ceRNA and Regulates AML Cell Proliferation and Apoptosis via miR136-5p/MCM5 Axis

2020 ◽  
Author(s):  
Chen Liu ◽  
Liang Zhong ◽  
Chenlan Shen ◽  
Xuan Chu ◽  
Xu Luo ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Noncoding Rna ◽  
Colorectal Neoplasia ◽  
Luciferase Reporter ◽  
Cell Cycle Distribution ◽  
Risc Complex ◽  
Proliferation And Apoptosis ◽  
Rna Immunoprecipitation ◽  
Cell Processes

Abstract Background: Increasing evidence demonstrated that long noncoding RNAs (lncRNAs) act as important factors in the regulation of cell processes and tumorigenesis. The long-noncoding RNA colorectal neoplasia differentially expressed (CRNDE) gene has been found to be related to several types of cancer. Although CRNDE is highly expressed in AML, its mechanism of action in acute myeloid leukemia (AML) is unknown.Methods: The expression levels of CRNDE and miR-136-5p mRNAs were measured by quantitative real-time PCR. The effects of CRNDE knockdown on cell proliferation was assessed by the CCK8 assay, while apoptosis and cell cycle distribution were analyzed by flow cytometry. The expression of proteins related to cell cycle, cell apoptosis and MCM5 were analyzed by Western blotting. The luciferase reporter assay was used to confirm the interaction between CRNDE and miR-136-5p and between MCM5 and miR-136-5p in AML. The RNA immunoprecipitation assay was used to verify whether CRNDE exists in the miRNA mediated RISC complex.Results: In this study, we used GEPIA database to confirm that CRNDE expression was significantly upregulated in AML samples. The silencing of CRNDE inhibited AML cells’ proliferation ability, increased AML cells’ apoptotic rate and arrested AML cells at the G1 phase of the cell cycle. Mechanistically, CRNDE served as a competing endogenous RNA (ceRNA) for miR-136-5p and upregulated MCM5 expression by sponging miR-136-5p. In addition, rescue assays revealed that the effects of CRNDE knockdown could be reversed by miR-136-5p inhibitors in AML cells. Conclusion: Our results demonstrate that the CRNDE-miR-136-5p-MCM5 axis modulates AML progression and provide a new regulatory network of CRNDE in AML.

scholarly journals MicroRNA-16 Promotes Ovarian Granulosa Cell Proliferation and Suppresses Apoptosis Through Targeting PDCD4 in Polycystic Ovarian Syndrome

2018 ◽  
Vol 48 (2) ◽  
pp. 670-682 ◽  
Author(s):  
Xiafei  Fu ◽  
Yuanli He ◽  
Xuefeng Wang ◽  
Dongxian Peng ◽  
Xiaoying Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Polycystic Ovarian Syndrome ◽  
Luciferase Reporter ◽  
Cell Cycle Distribution ◽  
Regulatory Relationship ◽  
Ovarian Cortex ◽  
Pdcd4 Expression ◽  
Ovarian Syndrome

Background/Aims: Several miRNAs have been reported to be involved in the pathogenesis of polycystic ovarian syndrome (PCOS). However, the biological roles of miR-16 and its molecular mechanisms in PCOS development remain to be elucidated. Methods: qRT-PCR was performed to detect the expression levels of miR-16 and programmed cell death protein 4 (PDCD4). GCs proliferation, cell cycle distribution and apoptosis were examined by MTT assay and flow cytometry analysis. Luciferase reporter assay and RIP assay were applied to confirm the regulatory relationship between miR-16 and PDCD4. Western blot was applied to measure the protein levels of PDCD4, PCNA and caspase-3. ELISA kits were used to determine the serum levels of steroids. Results: miR-16 expression was down-regulated in ovarian cortex tissues and serums of PCOS patients. PDCD4 expression was up-regulated in ovarian cortex tissues of PCOS patients. miR-16 overexpression facilitated cell proliferation, induced cell cycle progression, and inhibited apoptosis in GCs. Moreover, PDCD4 was a direct target of miR-16. Also, enforced expression of PDCD4 abated the effects of miR-16 on GCs growth and apoptosis. Additionally, testosterone resulted in a decrease of miR-16 expression and an increase of PDCD4 expression, thus blocking cell growth and enhanced apoptosis in GCs. Furthermore, miR-16 overexpression alleviated PCOS in vivo by regulating PDCD4. Conclusions: miR-16 promoted ovarian GCs proliferation and inhibited apoptosis through directly targeting PDCD4 in PCOS, contributing to a better understanding of the molecular mechanism of GCs dysregulation and providing a promising target in PCOS.

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