scholarly journals Circ_0084927 promotes cervical carcinogenesis by sponging miR-1179 that suppresses CDK2, a cell cycle-related gene

2020 ◽  
Author(s):  
Xinhua Qu ◽  
Liumei Zhu ◽  
Linlin Song ◽  
Shaohua Liu
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Regulatory Network ◽  
Inhibitory Effect ◽  
Cervical Carcinogenesis ◽  
Activation Assay ◽  
Cell Cycle Related Gene ◽  
Rna Immunoprecipitation ◽  
A Cell ◽  
Brdu Assay

Abstract Background: Cervical cancer (CC) is a highly malignant tumor. Evolving researches on CC have unveiled a concept that circRNA exerts important roles in CC progression. In this study, we mainly explored the role of a novel circRNA, circ_0084927, and its regulatory network in the development of CC.Methods: qRT-PCR was applied to evaluate the expression of circ_0084927, miR-1179 and CDK2 mRNA in CC tissues and cells. Dual-luciferase reporting experiments and RNA immunoprecipitation (RIP) assay were conducted to validate the target relationship of miR-1179 with circ_0084927 and CDK2 mRNA. CCK-8 and BrdU assay was used to evaluate CC cell proliferation. The adhesion and apoptosis phenotypes of CC cells were measured by cell-matrix adhesion and caspase 3 activation assay. Flow cytometry was employed to detect CC cell cycle.Results: Our results indicated that circ_0084927 was up-regulated in CC tissues and cells, and circ_0084927 silence inhibited CC cell proliferation and adhesion, while facilitating apoptosis as well as triggering cell cycle arrest. On the other hand, miR-1179 down-regulation appeared in CC tissues. Additionally, circ_0084927 abolished miR-1179’s inhibitory effects on cell proliferation and adhesion. Our study showed that CDK2 was up-regulated in CC tissues and played a cancer-promoting role. Furthermore, miR-1179 directly targeted CDK2, thereby inhibiting CDK2’s promotion on the malignant phenotypes of CC cells. circ_0084927 revoked the inhibitory effect of miR-1179 on CDK2 by sponging miR-1179.Conclusion: Circ_0084927 promoted cervical carcinogenesis by sequestering miR-1179 that directly targeted CDK2. Our results shed light on the circ_0084927/miR-1179/CDK2 regulatory network that strengthened CC aggressiveness, providing novel candidate targets for CC treatment.

scholarly journals Circ_0084927 promotes cervical carcinogenesis by sponging miR-1179 that suppresses CDK2, a cell cycle-related gene

2020 ◽  
Author(s):  
Xinhua Qu ◽  
Liumei Zhu ◽  
Linlin Song ◽  
Shaohua Liu
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Regulatory Network ◽  
Inhibitory Effect ◽  
Cervical Carcinogenesis ◽  
Activation Assay ◽  
Cell Cycle Related Gene ◽  
Rna Immunoprecipitation ◽  
A Cell ◽  
Brdu Assay

Abstract Background: Cervical cancer (CC) is a highly malignant tumor. Evolving researches on CC have unveiled a concept that circRNA exerts important roles in CC progression. In this study, we mainly explored the role of a novel circRNA, circ_0084927, and its regulatory network in the development of CC. Methods: qRT-PCR was applied to evaluate the expression of circ_0084927, miR-1179 and CDK2 mRNA in CC tissues and cells. Dual-luciferase reporting experiments and RNA immunoprecipitation (RIP) assay were conducted to validate the target relationship of miR-1179 with circ_0084927 and CDK2 mRNA. CCK-8 and BrdU assay was used to evaluate CC cell proliferation. The adhesion and apoptosis phenotypes of CC cells were measured by cell-matrix adhesion and caspase 3 activation assay. Flow cytometry was employed to detect CC cell cycle. Results: Our results indicated that circ_0084927 was up-regulated in CC tissues and cells, and circ_0084927 silence inhibited CC cell proliferation and adhesion, while facilitating apoptosis as well as triggering cell cycle arrest. On the other hand, miR-1179 down-regulation appeared in CC tissues. Additionally, circ_0084927 abolished miR-1179’s inhibitory effects on cell proliferation and adhesion. Our study showed that CDK2 was up-regulated in CC tissues and played a cancer-promoting role. Furthermore, miR-1179 directly targeted CDK2, thereby inhibiting CDK2’s promotion on the malignant phenotypes of CC cells. circ_0084927 revoked the inhibitory effect of miR-1179 on CDK2 by sponging miR-1179. Conclusion: Circ_0084927 promoted cervical carcinogenesis by sequestering miR-1179 that directly targeted CDK2. Our results shed light on the circ_0084927/miR-1179/CDK2 regulatory network that strengthened CC aggressiveness, providing novel candidate targets for CC treatment.

scholarly journals circ_0084927 promotes cervical carcinogenesis by sponging miR-1179 that suppresses CDK2, a cell cycle-related gene

2020 ◽  
Author(s):  
Xinhua Qu ◽  
Liumei Zhu ◽  
Linlin Song ◽  
Shaohua Liu
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Regulatory Network ◽  
Inhibitory Effect ◽  
Cervical Carcinogenesis ◽  
Activation Assay ◽  
Cell Cycle Related Gene ◽  
Rna Immunoprecipitation ◽  
A Cell ◽  
Brdu Assay

Abstract Background: Cervical cancer (CC) is a highly malignant tumor. found in the lowermost part of the womb. Evolving researchesstudies on CC have unveiled a conceptreported that circRNA exerts important rolesplays a crucial role in CC progression. In this study, we mainly exploredinvestigated the rolemain function of a novel circRNA, circ_0084927, and its regulatory network in theCC development of CC. Methods: qRT-PCR was applied to evaluate the expression of circ_0084927, miR-1179, and CDK2 mRNA in CC tissues and cells. Dual-luciferase reporting experiments and RNA immunoprecipitation (RIP) assay were conducted to validate the target relationship of miR-1179 with circ_0084927 and CDK2 mRNA. CCK-8 and BrdU assay wasassays were also used to evaluate CC cell proliferation. The adhesion and apoptosis phenotypes of CC cells were measured byusing cell-matrix adhesion and caspase 3 activation assay. Flow cytometry was also employed to detect the CC cell cycle. Results: Our results indicated that circ_0084927 was up-regulated in CC tissues and cells, and. Findings also revealed that circ_0084927 silence inhibited CC cell proliferation and adhesion, while facilitating apoptosis as well asand triggering cell cycle arrest. On the other handHowever, miR-1179 down-regulation appeared in CC tissues. Additionally,Apart from observing that circ_0084927 abolished miR-1179’s inhibitory effects on cell proliferation and adhesion. Our study showed, it was found that CDK2 was up-regulated in CC tissues and played awas instrumental in cancer-promoting role. Furthermore, promotion. Also observed was that miR-1179 directly targeted CDK2, thereby inhibiting CDK2’s promotion on the malignant phenotypes of CC cells. Lastly, results indicated that circ_0084927 revoked the inhibitory effect of miR-1179 on CDK2 by sponging miR-1179. Conclusion: Circcirc_0084927 promoted cervical carcinogenesis by sequestering miR-1179 that, which directly targeted CDK2. Our results shed light onalso provided novel candidate targets for CC treatment in that it revealed the circ_0084927/miR-1179/CDK2 regulatory network that strengthened CC aggressiveness, providing novel candidate targets for CC treatment..

Targeted Modulation of FAK/PI3K/PDK1/AKT and FAK/p53 Pathways by Cucurbitacin B for the Antiproliferation Effect Against Human Cholangiocarcinoma Cells

2020 ◽  
Vol 48 (06) ◽  
pp. 1475-1489
Author(s):  
Sirinapha Klungsaeng ◽  
Veerapol Kukongviriyapan ◽  
Auemduan Prawan ◽  
Sarinya Kongpetch ◽  
Laddawan Senggunprai
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Tyrosine Kinases ◽  
Molecular Mechanisms ◽  
Inhibitory Effect ◽  
Chemotherapeutic Agents ◽  
Cucurbitacin B ◽  
M Phase ◽  
Cell Cycle Disruption

Inadequate responses to traditional chemotherapeutic agents in cholangiocarcinoma (CCA) emphasize a requirement for new effective compounds for the treatment of this malignancy. This study aimed to investigate the antiproliferative property of cucurbitacin B on KKU-100 CCA cells. The determination of underlying molecular mechanisms was also carried out. The results revealed that cucurbitacin B suppressed growth and replicative ability to form colonies of CCA cells, suggesting the antiproliferative effect of this compound against the cells. Flow cytometry analysis demonstrated that the interfering effect of cucurbitacin B on the CCA cell cycle at the G2/M phase was accountable for its antiproliferation property. Accompanied with cell cycle disruption, cucurbitacin B altered the expression of proteins involved in the G2/M phase transition including downregulation of cyclin A, cyclin D1, and cdc25A, and upregulation of p21. Additional molecular studies demonstrated that cucurbitacin B suppressed the activation of focal adhesion kinase (FAK) which consequently resulted in inhibition of its kinase-dependent and kinase-independent downstream targets contributing to the regulation of cell proliferation including PI3K/PDK1/AKT and p53 proteins. In this study, the transient knockdown of FAK using siRNA was employed to ascertain the role of FAK in CCA cell proliferation. Finally, the effect of cucurbitacin B on upstream receptor tyrosine kinases regulating FAK activation was elucidated. The results showed that the inhibitory effect of cucurbitacin B on FAK activation in CCA cells is mediated via interference of EGFR and HER2 expression. Collectively, cucurbitacin B might be a promising drug for CCA treatment by targeting FAK protein.

scholarly journals The effects of 5α-dihydrotestosterone on the kinetics of cell proliferation in rat prostate

1974 ◽  
Vol 142 (3) ◽  
pp. 483-489 ◽  
Author(s):  
Barry Lesser ◽  
Nicholas Bruchovsky
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cellular Growth ◽  
Velocity Sedimentation ◽  
Growth Fraction ◽  
Subcutaneous Injections ◽  
Daughter Cells ◽  
A Cell ◽  
Rat Prostate ◽  
Kinetics Of

The regenerating rat prostate was used as an experimental model to determine the effects of 5α-dihydrotestosterone on certain parameters of cell proliferation, including the duration of the phases of the cell cycle and the size of the cellular growth fraction. Rats castrated 7 days previously were treated with daily subcutaneous injections of 5α-dihydrotestosterone for 14 days; 48h after the beginning of therapy, cells in the process of DNA synthesis were labelled with a single injection of radioactive thymidine and the progress of these cells through the division cycle was observed. Cell-cycle analysis was performed by fractionating prostatic nuclei according to their position in the cell cycle by using the technique of velocity sedimentation under unit gravity. The results indicate that during regeneration the cell population undergoes 1.8 doublings with a doubling time of 40h, and that the process involves almost four rounds of cell division with a cell-generation time of 20h. The growth fraction at any time is about 0.5, and about half the daughter cells produced do not re-enter the proliferative cycle. All cells present at the start of regeneration eventually undergo at least one division during the course of regeneration, although any given cell can divide from one to four times.

scholarly journals LncRNA HOXA-AS2 Promotes Oral Squamous Cell Proliferation, Migration, and Invasion via Upregulating EZH2 as an Oncogene

2021 ◽  
Vol 20 ◽  
pp. 153303382110391
Author(s):  
Zhen Zhao ◽  
Yan Xing ◽  
Fei Yang ◽  
Zhijun Zhao ◽  
Yupeng Shen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Squamous Cell ◽  
Inhibitory Effect ◽  
G1 Phase ◽  
Migration And Invasion ◽  
Tunel Staining ◽  
Cell Cycle Distribution ◽  
Induce Cell Cycle Arrest ◽  
Invasion And Migration

Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer worldwide. Accumulating evidence has shown that long noncoding RNAs (lncRNAs) serve important roles in the development of OSCC. The purpose of this study was to investigate the biological function and underlying regulatory mechanism of lncRNA homeobox A cluster antisense RNA2 (HOXA-AS2) in OSCC. RT-qPCR was performed to analyze the HOXA-AS2 expressions in human immortalized oral epithelial cell (HIOEC) line, human OSCC cell lines, and plasma. The expression of HOXA-AS2 and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) in Tca-8113 cells were knocked down or overexpressed by transfection with shRNA-HOXA-AS2 or pcDNA-EZH2, respectively. The interaction between HOXA-AS2 and EZH2 was validated by RNA immunoprecipitation assay. In addition, cell proliferation was assessed by CCK-8 and EdU assays. Cell cycle distribution was analyzed by flow cytometry. Cell migration and invasion were detected using wound healing and Transwell assays, respectively. Apoptosis was detected by TUNEL staining. The protein expression levels of cell cycle and apoptosis-related proteins were measured by western blot analysis. Compared with HIOEC cells, HOXA-AS2 expression in OSCC cells was upregulated. HOXA-AS2 knockdown significantly inhibited Tca-8113 cell proliferation, blocked the cell cycle by arresting cells in the G0/G1 phase, promoted apoptosis, and suppressed migration and invasion. In addition, HOXA-AS2 was predicted to directly target EZH2 and positively regulate EZH2 expression. EZH2 overexpression could reverse the inhibitory effect of HOXA-AS2 knockdown on the proliferation, migration, and invasion of Tca-8113 cells. In summary, the findings suggested that HOXA-AS2 may inhibit cell proliferation, invasion, and migration, induce cell cycle arrest in the G0/G1 phase, and increase cell apoptosis by targeting EZH2. The research indicated that HOXA-AS2/EZH2 axis may play a key role in the development of OSCC.

scholarly journals Identification of a novel circ_0018289/miR-183-5p/TMED5 regulatory network in cervical cancer development

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Heng Zou ◽  
Huijia Chen ◽  
Shuaibin Liu ◽  
Xiaoling Gan
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Cell Apoptosis ◽  
Regulatory Network ◽  
Molecular Basis ◽  
Tube Formation ◽  
Cancer Development ◽  
Cervical Carcinogenesis ◽  
Cervical Cancer Development

Abstract Background Circular RNAs (circRNAs) are increasingly implicated in regulating human carcinogenesis. Previous work showed the oncogenic activity of circ_0018289 in cervical cancer. However, the molecular basis underlying the modulation of circ_0018289 in cervical carcinogenesis is still not fully understood. Methods The levels of circ_0018289, microRNA (miR)-183-5p, and transmembrane p24 trafficking protein 5 (TMED5) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Ribonuclease (RNase) R and subcellular localization assays were used to characterize circ_0018289. Cell proliferation was detected by the Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (Edu) assays. Cell apoptosis and tube formation were assessed by flow cytometry and tube formation assays, respectively. A dual-luciferase reporter assay was performed to confirm the direct relationship between miR-183-5p and circ_0018289 or TMED5. The role of circ_0018289 in tumor growth was gauged by mouse xenograft experiments. Results Circ_0018289 was overexpressed in cervical cancer tissues and cells. Circ_0018289 silencing impeded cell proliferation, enhanced cell apoptosis, and suppressed angiogenesis in vitro, as well as diminished tumor growth in vivo. Mechanistically, circ_0018289 targeted and regulated miR-183-5p by binding to miR-183-5p, and circ_0018289 regulated cervical cancer development and angiogenesis partially through miR-183-5p. Moreover, TMED5 was directly targeted and inhibited by miR-183-5p through the perfect complementary sites in TMED5 3′UTR, and TMED5 knockdown phenocopied miR-183-5p overexpression in suppressing cervical cancer development and angiogenesis. Furthermore, circ_0018289 induced TMED5 expression by competitively binding to shared miR-183-5p. Conclusion Our observations identified the circ_0018289/miR-183-5p/TMED5 regulatory network as a novel molecular basis underlying the modulation of cervical carcinogenesis.

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.

c-Jun N-terminal kinase/c-Jun inhibits fibroblast proliferation by negatively regulating the levels of stathmin/oncoprotein 18

2010 ◽  
Vol 430 (2) ◽  
pp. 345-354 ◽  
Author(s):  
Yvonne Y. C. Yeap ◽  
Ivan H. W. Ng ◽  
Bahareh Badrian ◽  
Tuong-Vi Nguyen ◽  
Yan Y. Yip ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cellular Proliferation ◽  
Cell System ◽  
Tumour Suppressor Protein ◽  
Oncoprotein 18 ◽  
A Cell ◽  
Cancer Types ◽  
Type C ◽  
Interfering Rna

The JNKs (c-Jun N-terminal kinases) are stress-activated serine/threonine kinases that can regulate both cell death and cell proliferation. We have developed a cell system to control JNK re-expression at physiological levels in JNK1/2-null MEFs (murine embryonic fibroblasts). JNK re-expression restored basal and stress-activated phosphorylation of the c-Jun transcription factor and attenuated cellular proliferation with increased cells in G1/S-phase of the cell cycle. To explore JNK actions to regulate cell proliferation, we evaluated a role for the cytosolic protein, STMN (stathmin)/Op18 (oncoprotein 18). STMN, up-regulated in a range of cancer types, plays a crucial role in the control of cell division through its regulation of microtubule dynamics of the mitotic spindle. In JNK1/2-null or c-Jun-null MEFs or cells treated with c-Jun siRNA (small interfering RNA), STMN levels were significantly increased. Furthermore, a requirement for JNK/cJun signalling was demonstrated by expression of wild-type c-Jun, but not a phosphorylation-defective c-Jun mutant, being sufficient to down-regulate STMN. Critically, shRNA (small hairpin RNA)-directed STMN down-regulation in JNK1/2-null MEFs attenuated proliferation. Thus JNK/c-Jun regulation of STMN levels provides a novel pathway in regulation of cell proliferation with important implications for understanding the actions of JNK as a physiological regulator of the cell cycle and tumour suppressor protein.

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