Tristetraprolin induces cell cycle arrest in breast tumor cells through targeting AP-1/c-Jun and NF-κB pathway

Abstract Background: Dysregulation of cell cycle progression is one of the common features of human cancer cells, however, its mechanism remains unclear. This study aims to clarify the role and the underlying mechanisms of Roquin1 in cell cycle arrest induction in breast cancer.Methods: Public cancer databases were analyzed to identify the expression pattern of Roquin1 in human breast cancers and the significant association with patient survival. Quantitative real-time PCR and western blots were performed to detect the expression of Roquin1 in breast cancer samples and cell lines. Cell counting, MTT assay, flow cytometry, and in vivo study were conducted to investigate the effects of Roquin1 on cell proliferation, cell cycle progression and tumor progression. RNA-sequencing was applied to identify the differential genes and pathways regulated by Roquin1. RNA immunoprecipitation assay, luciferase reporter assay, mRNA half-life detection, RNA affinity binding assay, and RIP-ChIP were used to explore the molecular mechanisms of Roquin1.Results: We showed that Roquin1 expression in breast cancer tissues and cell lines was inhibited, and the reduction in Roquin1 expression was associated with poor overall survival and relapse free survival of patients with breast cancer. Roquin1 overexpression inhibited breast cancer cell proliferation and induced G1/S cell cycle arrest without causing significant apoptosis. In contrast, knockdown of Roquin1 promoted breast cancer cell growth and cycle progression. Moreover, in vivo induction of Roquin1 by adenovirus significantly suppressed breast tumor growth and metastasis. Mechanistically, Roquin1 selectively destabilizing cell cycle–promoting genes, including Cyclin D1, Cyclin E1, cyclin dependent kinase 6 (CDK6) and minichromosome maintenance 2 (MCM2) through targeting the stem–loop structure in the 3’untranslated region (3’UTR) of mRNAs via its ROQ domain, leading to the downregulation of cell cycle–promoting mRNAs.Conclusions: Our findings demonstrated that Roquin1 was a novel breast tumor suppressor and could induce G1/S cell cycle arrest by selectively downregulating the expression of cell cycle–promoting genes, which might as a potential molecular target for breast cancer treatment.

Download Full-text

Progression of LNCaP Prostate Tumor Cells during Androgen Deprivation: Hormone-Independent Growth, Repression of Proliferation by Androgen, and Role for p27Kip1 in Androgen-Induced Cell Cycle Arrest

Molecular Endocrinology ◽

10.1210/mend.12.7.0136 ◽

1998 ◽

Vol 12 (7) ◽

pp. 941-953 ◽

Cited By ~ 103

Author(s):

John M. Kokontis ◽

Nissim Hay ◽

Shutsung Liao

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Tumor Cells ◽

Androgen Deprivation ◽

Prostate Tumor ◽

Cycle Arrest ◽

Prostate Tumor Cells

Download Full-text

Novel Tools to Analyze the Function of Salmonella Effectors Show That SvpB Ectopic Expression Induces Cell Cycle Arrest in Tumor Cells

PLoS ONE ◽

10.1371/journal.pone.0078458 ◽

2013 ◽

Vol 8 (10) ◽

pp. e78458 ◽

Cited By ~ 12

Author(s):

Beatriz Mesa-Pereira ◽

Carlos Medina ◽

Eva María Camacho ◽

Amando Flores ◽

Eduardo Santero

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Tumor Cells ◽

Ectopic Expression ◽

Cycle Arrest

Download Full-text

Roquin1 inhibits the proliferation of breast cancer cells by inducing G1/S cell cycle arrest via selectively destabilizing the mRNAs of cell cycle–promoting genes

10.21203/rs.3.rs-53499/v2 ◽

2020 ◽

Author(s):

Wenbao Lu ◽

Meicen Zhou ◽

Bing Wang ◽

Xueting Liu ◽

Bingwei Li

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Proliferation ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Breast Tumor ◽

Cell Cycle Progression ◽

Cycle Progression ◽

Cycle Arrest

Abstract Background: Dysregulation of cell cycle progression is a common feature of human cancer cells; however, its mechanism remains unclear. This study aims to clarify the role and the underlying mechanisms of Roquin1 in cell cycle arrest in breast cancer.Methods: Public cancer databases were analyzed to identify the expression pattern of Roquin1 in human breast cancers and its association with patient survival. Quantitative real-time PCR and Western blots were performed to detect the expression of Roquin1 in breast cancer samples and cell lines. Cell counting, MTT assays, flow cytometry, and in vivo analyses were conducted to investigate the effects of Roquin1 on cell proliferation, cell cycle progression and tumor progression. RNA sequencing was applied to identify the differentially expressed genes regulated by Roquin1. RNA immunoprecipitation assay, luciferase reporter assay, mRNA half-life detection, RNA affinity binding assay, and RIP-ChIP were used to explore the molecular mechanisms of Roquin1.Results: We showed that Roquin1 expression in breast cancer tissues and cell lines was inhibited, and the reduction in Roquin1 expression was associated with poor overall survival and relapse-free survival of patients with breast cancer. Roquin1 overexpression inhibited cell proliferation and induced G1/S cell cycle arrest without causing significant apoptosis. In contrast, knockdown of Roquin1 promoted cell growth and cycle progression. Moreover, in vivo induction of Roquin1 by adenovirus significantly suppressed breast tumor growth and metastasis. Mechanistically, Roquin1 selectively destabilizes cell cycle–promoting genes, including Cyclin D1, Cyclin E1, cyclin dependent kinase 6 (CDK6) and minichromosome maintenance 2 (MCM2), by targeting the stem–loop structure in the 3' untranslated region (3'UTR) of mRNAs via its ROQ domain, leading to the downregulation of cell cycle–promoting mRNAs.Conclusions: Our findings demonstrated that Roquin1 is a novel breast tumor suppressor and could induce G1/S cell cycle arrest by selectively downregulating the expression of cell cycle–promoting genes, which might be a potential molecular target for breast cancer treatment.

Download Full-text

Roquin1 inhibits the proliferation of breast cancer cells by inducing G1/S cell cycle arrest via selectively destabilizing the mRNAs of cell cycle–promoting genes

10.21203/rs.3.rs-53499/v3 ◽

2020 ◽

Author(s):

Wenbao Lu ◽

Meicen Zhou ◽

Bing Wang ◽

Xueting Liu ◽

Bingwei Li

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Proliferation ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Breast Tumor ◽

Cell Cycle Progression ◽

Cycle Progression ◽

Cycle Arrest

Abstract Background: Dysregulation of cell cycle progression is one of the common features of human cancer cells, however, its mechanism remains unclear. This study aims to clarify the role and the underlying mechanisms of Roquin1 in cell cycle arrest induction in breast cancer. Methods: Public cancer databases were analyzed to identify the expression pattern of Roquin1 in human breast cancers and the significant association with patient survival. Quantitative real-time PCR and western blots were performed to detect the expression of Roquin1 in breast cancer samples and cell lines. Cell counting, MTT assay, flow cytometry, and in vivo study were conducted to investigate the effects of Roquin1 on cell proliferation, cell cycle progression and tumor progression. RNA-sequencing was applied to identify the differential genes and pathways regulated by Roquin1. RNA immunoprecipitation assay, luciferase reporter assay, mRNA half-life detection, RNA affinity binding assay, and RIP-ChIP were used to explore the molecular mechanisms of Roquin1. Results: We showed that Roquin1 expression in breast cancer tissues and cell lines was inhibited, and the reduction in Roquin1 expression was associated with poor overall survival and relapse free survival of patients with breast cancer. Roquin1 overexpression inhibited breast cancer cell proliferation and induced G1/S cell cycle arrest without causing significant apoptosis. In contrast, knockdown of Roquin1 promoted breast cancer cell growth and cycle progression. Moreover, in vivo induction of Roquin1 by adenovirus significantly suppressed breast tumor growth and metastasis. Mechanistically, Roquin1 selectively destabilizing cell cycle–promoting genes, including Cyclin D1, Cyclin E1, cyclin dependent kinase 6 (CDK6) and minichromosome maintenance 2 (MCM2) through targeting the stem–loop structure in the 3’untranslated region (3’UTR) of mRNAs via its ROQ domain, leading to the downregulation of cell cycle–promoting mRNAs. Conclusions: Our findings demonstrated that Roquin1 was a novel breast tumor suppressor and could induce G1/S cell cycle arrest by selectively downregulating the expression of cell cycle–promoting genes, which might as a potential molecular target for breast cancer treatment.

Download Full-text

ChemInform Abstract: A Novel Aminothiazole Derivative Induces Apoptosis and Cell Cycle Arrest in Tumor Cells.

ChemInform ◽

10.1002/chin.201112122 ◽

2011 ◽

Vol 42 (12) ◽

pp. no-no

Author(s):

Minghua Li ◽

Changwon Oh ◽

Jun Seok Park ◽

Seung Wook Ham

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Tumor Cells ◽

Cycle Arrest

Download Full-text

The p75NTR tumor suppressor induces cell cycle arrest facilitating caspase mediated apoptosis in prostate tumor cells

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2006.01.073 ◽

2006 ◽

Vol 341 (4) ◽

pp. 1184-1192 ◽

Cited By ~ 45

Author(s):

Fatima Khwaja ◽

Arshia Tabassum ◽

Jeff Allen ◽

Daniel Djakiew

Keyword(s):

Cell Cycle ◽

Tumor Suppressor ◽

Cell Cycle Arrest ◽

Tumor Cells ◽

Prostate Tumor ◽

Cycle Arrest ◽

Prostate Tumor Cells

Download Full-text

The Methanol Extract ofAngelica sinensisInduces Cell Apoptosis and Suppresses Tumor Growth in Human Malignant Brain Tumors

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/394636 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Yu-Ling Lin ◽

Wen-Lin Lai ◽

Horng-jyh Harn ◽

Pei-Hsiu Hung ◽

Ming-Chang Hsieh ◽

...

Keyword(s):

Cell Cycle ◽

Brain Tumor ◽

Brain Tumors ◽

Cell Cycle Arrest ◽

Tumor Cells ◽

Methanol Extract ◽

Cycle Arrest ◽

Anticancer Effects ◽

Brain Tumor Cells

Glioblastoma multiforme (GBM) is a highly vascularized and invasive neoplasm. The methanol extract ofAngelica sinensis(AS-M) is commonly used in traditional Chinese medicine to treat several diseases, such as gastric mucosal damage, hepatic injury, menopausal symptoms, and chronic glomerulonephritis. AS-M also displays potency in suppressing the growth of malignant brain tumor cells. The growth suppression of malignant brain tumor cells by AS-M results from cell cycle arrest and apoptosis. AS-M upregulates expression of cyclin kinase inhibitors, including p16, to decrease the phosphorylation of Rb proteins, resulting in arrest at the G0-G1phase. The expression of the p53 protein is increased by AS-M and correlates with activation of apoptosis-associated proteins. Therefore, the apoptosis of cancer cells induced by AS-M may be triggered through the p53 pathway. Inin vivostudies, AS-M not only suppresses the growth of human malignant brain tumors but also significantly prolongs patient survival. In addition, AS-M has potent anticancer effects involving cell cycle arrest, apoptosis, and antiangiogenesis. Thein vitroandin vivoanticancer effects of AS-M indicate that this extract warrants further investigation and potential development as a new antibrain tumor agent, providing new hope for the chemotherapy of malignant brain cancer.

Download Full-text