Downregulation of ROS-FIG inhibits cell proliferation, colony-formation, cell cycle progression, migration and invasion, while inducing apoptosis in intrahepatic cholangiocarcinoma cells

Background: Gliomas result in the highest morbidity and mortality rates of intracranial primary central nervous system tumors because of their aggressive growth characteristics and high postoperative recurrence. They are characterized by genetic instability, intratumoral histopathological variability and unpredictable clinical behavior in patients. Proliferation is a key aspect of the clinical progression of malignant gliomas, complicating complete surgical resection and enabling tumor regrowth and further proliferation of the surviving tumor cells. Methods: The expression of Fstl1 was detected by western blotting and qRT-PCR. We used cell proliferation and colony formation assays to measure proliferation. Then, flow cytometry was used to analyze cell cycle progression. The expression of Fstl1, p-Smad1/5/8 and p21 in GBM tissue sections was evaluated using immunohistochemical staining. Furthermore, we used coimmunoprecipitation (Co-IP) and immunoprecipitation to validate the relationship between Fstl1, BMP4 and BMPR2. Finally, we used orthotopic xenograft studies to measure the growth of tumors in vivo. Results: We found that follistatin-like 1 (Fstl1) was upregulated in high-grade glioma specimens and that its levels correlated with poor prognosis. Fstl1 upregulation increased cell proliferation, colony formation and cell cycle progression, while its knockdown inhibited these processes. Moreover, Fstl1 interacted with bone morphogenetic protein (BMP) 4, but not BMP receptor (BMPR) 2, and competitively inhibited their association. Furthermore, Fstl1 overexpression suppressed the activation of the BMP4/Smad1/5/8 signaling pathway, while BMP4 overexpression reversed this effect. Conclusion: Our study demonstrated that Fstl1 promoted glioma growth through the BMP4/Smad1/5/8 signaling pathway, and these findings suggest potential new glioblastoma treatment strategies.

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FOXM1 modulates docetaxel resistance in prostate cancer by regulating KIF20A

Cancer Cell International ◽

10.1186/s12935-020-01631-y ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Hongbo Yu ◽

Zheng Xu ◽

Maomao Guo ◽

Weiwan Wang ◽

Weican Zhang ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Cycle ◽

Cell Proliferation ◽

Cell Apoptosis ◽

Cell Cycle Progression ◽

Migration And Invasion ◽

Cycle Progression ◽

Docetaxel Resistance ◽

Apoptosis Protein

Abstract Background Docetaxel resistance affects prognosis in advanced prostate cancer (PCa). The precise mechanisms remain unclear. Transcription factor Forkhead box M1 (FOXM1), which participates in cell proliferation and cell cycle progression, has been reported to affect the sensitivity of chemotherapy. This study explores the role of FOXM1 in PCa docetaxel resistance and its association with kinesin family member 20 A (KIF20A), which is known to promote therapeutic resistance in some cancers. Methods We monitored cell growth using MTT and colony formation assays, and cell apoptosis and cell cycle progression using flow cytometry. Wound-healing and transwell assays were used to detect cell invasion and migration. mRNA and protein expression were analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. We monitored FOXM1 binding to the KIF20A promoter using a ChIP assay. Tumorigenicity in nude mice was used to assess in vivo tumorigenicity. Results FOXM1 knockdown induced cell apoptosis and G2/M cell cycle arrest, suppressing cell migration and invasion in docetaxel-resistant PCa cell lines (DU145-DR and VCaP-DR). Exogenous FOXM1 overexpression was found in their parental cells. Specific FOXM1 inhibitor thiostrepton significantly weakened docetaxel resistance in vitro and in vivo. We also found that FOXM1 and KIF20A exhibited consistent and highly correlated overexpression in PCa cells and tissues. FOXM1 also regulated KIF20A expression at the transcriptional level by acting directly on a Forkhead response element (FHRE) in its promoter. KIF20A overexpression could partially reverse the effect on cell proliferation, cell cycle proteins (cyclinA2, cyclinD1 and cyclinE1) and apoptosis protein (bcl-2 and PARP) of FOXM1 depletion. Conclusions Our findings indicate that highly expressed FOXM1 may help promote docetaxel resistance by inducing KIF20A expression, providing insight into novel chemotherapeutic strategies for combatting PCa docetaxel resistance.

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High Expression of ITGA3 Promotes Proliferation and Cell Cycle Progression and Indicates Poor Prognosis in Intrahepatic Cholangiocarcinoma

BioMed Research International ◽

10.1155/2018/2352139 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 7

Author(s):

Yu Huang ◽

Yang Kong ◽

Lufei Zhang ◽

Tianyu He ◽

Xiaohu Zhou ◽

...

Keyword(s):

Cell Cycle ◽

Cell Surface ◽

Cell Lines ◽

Intrahepatic Cholangiocarcinoma ◽

Cell Cycle Progression ◽

Malignant Tumors ◽

Migration And Invasion ◽

Integrin Subunit ◽

Surface Adhesion ◽

Cycle Progression

Integrin subunit alpha 3 (ITGA3) interacts with a beta 1 subunit to form a member of the integrin family. Integrins are heterodimeric integral membrane proteins that serve as cell surface adhesion proteins. In this research, we investigated the biological function of this protein in human intrahepatic cholangiocarcinoma (ICC) for the first time. Here, using Western blotting and immunohistochemistry assays, we discovered that ITGA3 was overexpressed in ICC cell lines and ICC patients. Moreover, we found ITGA3 expression correlated with several clinicopathological features, including tumor size, lymph node metastasis, and the TNM stage. Patients with high ITGA3 expression underwent a worse prognosis after complete resection compared with patients with low ITGA3 expression in terms of overall survival. Furthermore, we demonstrated that ITGA3 could significantly promote ICC cell proliferation and cell cycle progression in vitro. However, as a classical cell surface adhesion molecule, we found ITGA3 correlated negatively with the migration and invasion of ICC cell lines, which differs from other malignant tumors. Generally, these findings suggest that ITGA3 may play a role as a potential oncogene in ICC and suppression of ITGA3 expression may establish a novel target for guiding the therapy of ICC patients.

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FOXM1 modulates docetaxel resistance in prostate cancer by regulating KIF20A

10.21203/rs.3.rs-17966/v3 ◽

2020 ◽

Author(s):

Hongbo Yu ◽

Zheng Xu ◽

Maomao Guo ◽

Weiwan Wang ◽

Weican Zhang ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Cycle ◽

Cell Proliferation ◽

Cell Apoptosis ◽

Cell Cycle Progression ◽

Migration And Invasion ◽

Cycle Progression ◽

Docetaxel Resistance ◽

Apoptosis Protein

Abstract Background: Docetaxel resistance affects prognosis in advanced prostate cancer (PCa). The precise mechanisms remain unclear. The transcription factor Forkhead box M1 (FOXM1), which participates in cell proliferation and cell cycle progression, has been reported to affect the sensitivity of chemotherapy. This study explores the role of FOXM1 in PCa docetaxel resistance and its association with kinesin family member 20 A (KIF20A), which is known to promote therapeutic resistance in some cancers.Methods: We monitored cell growth using MTT and colony formation assays, and cell apoptosis and cell cycle progression using flow cytometry. Wound-healing and transwell assays were used to detect cell invasion and migration. mRNA and protein expression were analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. We monitored FOXM1 binding to the KIF20A promoter using the ChIP assay. Tumorigenicity in nude mice was used to assess in vivo tumorigenicity.Results: FOXM1 knockdown induced cell apoptosis and G2/M cell cycle arrest, suppressing cell migration and invasion in docetaxel-resistant PCa cell lines (DU145-DR and VCaP-DR). Exogenous FOXM1 overexpression was found in their parental cells. Specific FOXM1 inhibitor thiostrepton significantly weakened docetaxel resistance in vitro and in vivo. We also found FOXM1 and KIF20A exhibited consistent and highly correlated overexpression in PCa cells and tissues. FOXM1 also regulated KIF20A expression at the transcriptional level by acting directly on a Forkhead response element (FHRE) in its promoter. KIF20A overexpression could partially reverse the effect on cell proliferation, cell cycle proteins (cyclinA2, cyclinD1 and cyclinE1) and apoptosis protein (bcl-2 and PARP) of FOXM1 depletion.Conclusions: Our findings indicate highly expressed FOXM1 may help promote docetaxel resistance by inducing KIF20A expression, providing insight into novel chemotherapeutic strategies for combatting PCa docetaxel resistance.

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Knockdown of receptor tyrosine kinase-like orphan receptor 2 inhibits cell proliferation and colony formation in osteosarcoma cells by inducing arrest in cell cycle progression

Oncology Letters ◽

10.3892/ol.2015.3797 ◽

2015 ◽

Vol 10 (6) ◽

pp. 3705-3711 ◽

Cited By ~ 8

Author(s):

JIANJUN HUANG ◽

YING SHI ◽

HUI LI ◽

DUNYONG TAN ◽

MEISONGZHU YANG ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Tyrosine Kinase ◽

Receptor Tyrosine Kinase ◽

Colony Formation ◽

Cell Cycle Progression ◽

Orphan Receptor ◽

Osteosarcoma Cells ◽

Cycle Progression

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MCM6 indicates adverse tumor features and poor outcomes and promotes G1/S cell cycle progression in neuroblastoma

BMC Cancer ◽

10.1186/s12885-021-08344-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yaoyao Gu ◽

Xiaoxiao Hu ◽

Xiaowei Liu ◽

Cheng Cheng ◽

Kai Chen ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Western Blotting ◽

Cell Cycle Progression ◽

Neuroblastoma Cell ◽

Neuroblastoma Cells ◽

Tumor Stage ◽

Migration And Invasion ◽

Rna Seq ◽

Cycle Progression

Abstract Background Minichromosome maintenance complex component 6 (MCM6), as an important replication permission factor, is involved in the pathogenesis of various tumors. Here we studied the expression of MCM6 in neuroblastoma and its influence on tumor characteristics and prognosis. Methods Publicly available datasets were used to explore the influence of the differential expression of MCM6 on neuroblastoma tumor stage, risk and prognosis. In cell experiments, human neuroblastoma cell lines SK-N-SH and SK-N-BE [ (2)] were utilized to verify the ability of MCM6 to promote cell proliferation, migration and invasion. We further explored the possible molecular mechanism of MCM6 affecting the phenotype of neuroblastoma cells by mutual verification of RNA-seq and western blotting, and flow cytometry to inquire about its potential specific roles in the cell cycle. Results Through multiple datasets mining, we found that high expression of MCM6 was positively correlated with elevated tumor stage, high risk and poor prognosis in neuroblastoma. At the cellular level, neuroblastoma cell proliferation, migration and invasion were significantly inhibited after MCM6 was interfered by siRNA. Mutual verification of RNA-seq and western blotting suggested that the downstream cell cycle-related genes were differentially expressed after MCM6 interference. Flow cytometric analysis revealed that neuroblastoma cells were blocked in G1/S phase after MCM6 interference. Conclusion MCM6 is considered to be the driving force of G1/S cell cycle progression, and it is also a prognostic marker and a potential novel therapeutic target in neuroblastoma.

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FOXM1 modulates docetaxel resistance in prostate cancer by regulating KIF20A

10.21203/rs.3.rs-17966/v4 ◽

2020 ◽

Author(s):

Hongbo Yu ◽

Zheng Xu ◽

Maomao Guo ◽

Weiwan Wang ◽

Weican Zhang ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Cycle ◽

Cell Proliferation ◽

Cell Apoptosis ◽

Cell Cycle Progression ◽

Migration And Invasion ◽

Cycle Progression ◽

Docetaxel Resistance ◽

Apoptosis Protein

Abstract Background: Docetaxel resistance affects prognosis in advanced prostate cancer (PCa). The precise mechanisms remain unclear. Transcription factor Forkhead box M1 (FOXM1), which participates in cell proliferation and cell cycle progression, has been reported to affect the sensitivity of chemotherapy. This study explores the role of FOXM1 in PCa docetaxel resistance and its association with kinesin family member 20 A (KIF20A), which is known to promote therapeutic resistance in some cancers.Methods: We monitored cell growth using MTT and colony formation assays, and cell apoptosis and cell cycle progression using flow cytometry. Wound-healing and transwell assays were used to detect cell invasion and migration. mRNA and protein expression were analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. We monitored FOXM1 binding to the KIF20A promoter using a ChIP assay. Tumorigenicity in nude mice was used to assess in vivo tumorigenicity.Results: FOXM1 knockdown induced cell apoptosis and G2/M cell cycle arrest, suppressing cell migration and invasion in docetaxel-resistant PCa cell lines (DU145-DR and VCaP-DR). Exogenous FOXM1 overexpression was found in their parental cells. Specific FOXM1 inhibitor thiostrepton significantly weakened docetaxel resistance in vitro and in vivo. We also found that FOXM1 and KIF20A exhibited consistent and highly correlated overexpression in PCa cells and tissues. FOXM1 also regulated KIF20A expression at the transcriptional level by acting directly on a Forkhead response element (FHRE) in its promoter. KIF20A overexpression could partially reverse the effect on cell proliferation, cell cycle proteins (cyclinA2, cyclinD1 and cyclinE1) and apoptosis protein (bcl-2 and PARP) of FOXM1 depletion.Conclusions: Our findings indicate that highly expressed FOXM1 may help promote docetaxel resistance by inducing KIF20A expression, providing insight into novel chemotherapeutic strategies for combatting PCa docetaxel resistance.

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Circ_0084582 Facilitates Cell Growth, Migration, Invasion, and Angiopoiesis in Osteosarcoma via Mediating the miR-485-3p/JAG1 Axis

Frontiers in Genetics ◽

10.3389/fgene.2021.690956 ◽

2021 ◽

Vol 12 ◽

Author(s):

Peng Gao ◽

Xincheng Zhao ◽

Keying Yu ◽

Ziqiang Zhu

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Cell Cycle Progression ◽

Protein Detection ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Circular Rnas ◽

Reaction Cell ◽

Cycle Progression

Osteosarcoma (OS) is the most representative bone cancer, and circular RNAs serve as pivotal regulators in the progression of OS. This research was designed to explore the role and functional mechanism of circ_0084582 in OS. Circ_0084582, microRNA-485-3p (miR-485-3p), and Jagged1 (JAG1) levels were measured by quantitative real-time polymerase chain reaction. Cell proliferation was examined via 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Cell cycle progression was analyzed by flow cytometry. Wound healing and transwell assays were performed for evaluating cell migration and invasion. Angiopoiesis was assessed using the tube formation assay. Protein detection was conducted using Western blot. The target relation was identified by the dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA pull-down assay. A xenograft experiment was applied for analyzing the effect of circ_0084582 on OS in vivo. Circ_0084582 was highly expressed in OS tissues and cells. Circ_0084582 knockdown reduced cell proliferation, cell cycle progression, migration, invasion, and angiopoiesis of OS cells. JAG1 was upregulated in OS, and its overexpression reversed the effects of circ_0084582 knockdown on OS cells. Circ_0084582 targeted miR-485-3p, and miR-485-3p targeted JAG1, and circ_0084582 could affect the JAG1 level by sponging miR-485-3p. The function of circ_0084582 in OS progression was also achieved by sponging miR-485-3p. Circ_0084582 knockdown decreased OS growth in vivo partly by the miR-485-3p–mediated JAG1 downregulation. These results indicate that circ_0084582 functions as a tumorigenic factor in OS via the regulation of miR-485-3p/JAG1 axis.

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Proteomic Analysis Reveals That Placenta-Specific Protein 9 Inhibits Proliferation and Stimulates Motility of Human Bronchial Epithelial Cells

Frontiers in Oncology ◽

10.3389/fonc.2021.628480 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hai-Xia Wang ◽

Xu-Hui Qin ◽

Jinhua Shen ◽

Qing-Hua Liu ◽

Yun-Bo Shi ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Epithelial Cells ◽

Cell Motility ◽

Cell Cycle Progression ◽

Specific Protein ◽

Pulmonary Diseases ◽

Migration And Invasion ◽

Cycle Progression ◽

Bronchial Epithelial

Placenta-specific protein 9 (PLAC9) is a putative secretory protein that was initially identified in the placenta and is involved in cell proliferation and motility. Bioinformatics analyses revealed that PLAC9 is repressed in lung cancers (LCs), especially lung adenocarcinomas, compared to that in the paired adjacent normal tissues, indicating that PLAC9 might be involved in the pathogenesis of pulmonary diseases. To investigate the potential role of PLAC9 in the abnormal reprogramming of airway epithelial cells (AECs), a key cause of pulmonary diseases, we constructed a stable PLAC9-overexpressing human bronchial epithelial cell line (16HBE-GFP-Plac9). We utilized the proteomic approach isobaric tag for relative and absolute quantification (iTRAQ) to analyze the effect of PLAC9 on cellular protein composition. Gene ontology (GO) and pathway analyses revealed that GO terms and pathways associated with cell proliferation, cell cycle progression, and cell motility and migration were significantly enriched among the proteins regulated by PLAC9. Our in vitro results showed that PLAC9 overexpression reduced cell proliferation, altered cell cycle progression, and increased cell motility, including migration and invasion. Our findings suggest that PLAC9 inhibits cell proliferation through S phase arrest by altering the expression levels of cyclin/cyclin-dependent kinases (CDKs) and promotes cell motility, likely via the concerted actions of cyclins, E-cadherin, and vimentin. Since these mechanisms may underlie PLAC9-mediated abnormal human bronchial pathogenesis, our study provides a basis for the development of molecular targeted treatments for LCs.

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