Regulation of cell cycle progression by cyclooxygenase-2 in colorectal cancer; the role of the EP4 receptor, a novel therapeutic target

Pituitary Tumor Transforming Gene (PTTG) of human is known as a checkpoint gene in the middle and late stages of mitosis, and is also a proto-oncogene that promotes cell cycle progression. In the nucleus, PTTG works as securin in controlling the mid-term segregation of sister chromatids. Overexpression of PTTG, entering the nucleus with the help of PBF in pituitary adenomas, participates in the regulation of cell cycle, interferes with DNA repair, induces genetic instability, transactivates FGF-2 and VEGF and promotes angiogenesis and tumor invasion. Simultaneously, overexpression of PTTG induces tumor cell senescence through the DNA damage pathway, making pituitary adenoma possessing the potential self-limiting ability. To elucidate the mechanism of PTTG in the regulation of pituitary adenomas, we focus on both the positive and negative function of PTTG and find out key factors interacted with PTTG in pituitary adenomas. Furthermore, we discuss other possible mechanisms correlate with PTTG in pituitary adenoma initiation and development and the potential value of PTTG in clinical treatment.

Download Full-text

Restoration of miR-193a-5p and miR-146 a-5p Expression Induces G1 Arrest in Colorectal Cancer through Targeting of MDM2/p53

Advanced Pharmaceutical Bulletin ◽

10.15171/apb.2020.017 ◽

2019 ◽

Vol 10 (1) ◽

pp. 130-134 ◽

Cited By ~ 4

Author(s):

Saeed Noorolyai ◽

Elham Baghbani ◽

Leili Aghebati Maleki ◽

Amir Baghbanzadeh Kojabad ◽

Dariush Shanehbansdi ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Cell Cycle ◽

Tumor Suppressor ◽

Cell Cycle Progression ◽

Cyclin B ◽

G1 Arrest ◽

Cycle Progression ◽

Ht 29

Purpose: Colorectal cancer (CRC) remains a universal and lethal cancer owing to metastatic and relapsing disease. Currently, the role of microRNAs has been checked in tumorigeneses. Numerous studies have revealed that between the tumor suppressor miRNAs, the reduced expression of miR-146a-5p and -193a-5p in several cancers including CRC tissues are related with tumor progression and poor prognosis of patients. The purpose of this study is to examine the role of miR-146 a-5p and -193 a-5p in CRC cell cycle progression. Methods: The miR-193a-5p and -146 a-5p mimics were transfected into HT-29 CRC cells via jetPEI transfection reagent and their impact was assessed on p53, cyclin B, and NF-kB gene expression. The inhibitory effect of these miRNAs on cell cycle was assessed by flow cytometry. The consequence of miR-193a-5p and miR-146 a-5p on the protein expression level of Murine double minute 2 (MDM2) was assessed by western blotting. Results: miR193a-5p and -146a-5p regulated the expression of MDM2 protein and p53, cyclin B, and NF-kB gene expression in CRC cells. Treatment of HT-29 cells with miRNA-146a-5p and -193a-5p induced G1 cell cycle arrest. Conclusion: The findings of our study suggest that miR146a-5p and -193a-5p may act as a potential tumor suppressor by their influence on cell cycle progression in CRC cells. Thus, miRNA-146a-5p and -193a-5p restoration may be recommended as a potential therapeutic goal in the treatment of CRC patients.

Download Full-text

Role of PDE3A in regulation of cell cycle progression in mouse vascular smooth muscle cells and oocytes: implications in cardiovascular diseases and infertility

Current Opinion in Pharmacology ◽

10.1016/j.coph.2011.10.006 ◽

2011 ◽

Vol 11 (6) ◽

pp. 725-729 ◽

Cited By ~ 18

Author(s):

Najma Begum ◽

Weixing Shen ◽

Vincent Manganiello

Keyword(s):

Cell Cycle ◽

Smooth Muscle ◽

Cardiovascular Diseases ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Cell Cycle Progression ◽

Cycle Progression ◽

Regulation Of Cell Cycle

Download Full-text

The Role of Non-Coding RNAs in Controlling Cell Cycle Related Proteins in Cancer Cells

Frontiers in Oncology ◽

10.3389/fonc.2020.608975 ◽

2020 ◽

Vol 10 ◽

Author(s):

Soudeh Ghafouri-Fard ◽

Hamed Shoorei ◽

Farhad Tondro Anamag ◽

Mohammad Taheri

Keyword(s):

Cell Cycle ◽

Cell Cycle Progression ◽

Cycle Progression ◽

Cyclin Dependent Kinases ◽

Human Disorders ◽

Non Coding Rnas ◽

Regulation Of Cell Cycle ◽

Related Proteins ◽

Regulate Cell Cycle Progression

Cell cycle is regulated by a number of proteins namely cyclin-dependent kinases (CDKs) and their associated cyclins which bind with and activate CDKs in a phase specific manner. Additionally, several transcription factors (TFs) such as E2F and p53 and numerous signaling pathways regulate cell cycle progression. Recent studies have accentuated the role of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the regulation of cell cycle. Both lncRNAs and miRNAs interact with TFs participating in the regulation of cell cycle transition. Dysregulation of cell cycle regulatory miRNAs and lncRNAs results in human disorders particularly cancers. Understanding the role of lncRNAs, miRNAs, and TFs in the regulation of cell cycle would pave the way for design of anticancer therapies which intervene with the cell cycle progression. In the current review, we describe the role of lncRNAs and miRNAs in the regulation of cell cycle and their association with human malignancies.

Download Full-text

PBK/TOPK: A Therapeutic Target Worthy of Attention

Cells ◽

10.3390/cells10020371 ◽

2021 ◽

Vol 10 (2) ◽

pp. 371

Author(s):

Ziping Han ◽

Lingzhi Li ◽

Yuyou Huang ◽

Haiping Zhao ◽

Yumin Luo

Keyword(s):

Cell Cycle ◽

Therapeutic Target ◽

Cell Cycle Progression ◽

Killer Cell ◽

Adult Brain ◽

Clinical Settings ◽

Cycle Progression ◽

Pathological Conditions ◽

Potential Use

Accumulating evidence supports the role of PDZ-binding kinase (PBK)/T-lymphokine-activated killer-cell-originated protein kinase (TOPK) in mitosis and cell-cycle progression of mitotically active cells, especially proliferative malignant cells. PBK/TOPK was confirmed to be associated with the development, progression, and metastasis of malignancies. Therefore, it is a potential therapeutic target in cancer therapy. Many studies have been conducted to explore the clinical applicability of potent PBK/TOPK inhibitors. However, PBK/TOPK has also been shown to be overexpressed in normal proliferative cells, including sperm and neural precursor cells in the subventricular zone of the adult brain, as well as under pathological conditions, such as ischemic tissues, including the heart, brain, and kidney, and plays important roles in their physiological functions, including proliferation and self-renewal. Thus, more research is warranted to further our understanding of PBK/TOPK inhibitors before we can consider their applicability in clinical practice. In this study, we first review the findings, general features, and signaling mechanisms involved in the regulation of mitosis and cell cycle. We then review the functions of PBK/TOPK in pathological conditions, including tumors and ischemic conditions in the heart, brain, and kidney. Finally, we summarize the advances in potent and selective inhibitors and describe the potential use of PBK/TOPK inhibitors in clinical settings.

Download Full-text

circAPLP2 promotes colorectal cancer progression by upregulating HELLS by targeting miR-335-5p

Open Medicine ◽

10.1515/med-2021-0229 ◽

2021 ◽

Vol 16 (1) ◽

pp. 338-350

Author(s):

Rui Xiang ◽

Min Feng ◽

Xin Zhou ◽

Lihong Ma ◽

Ningfei Dong

Keyword(s):

Colorectal Cancer ◽

Cell Cycle ◽

Tumor Growth ◽

Nude Mice ◽

Solid Tumor ◽

Cell Apoptosis ◽

Colony Formation ◽

Cell Cycle Progression ◽

Cycle Progression

Abstract Background Colorectal cancer (CRC) is one of the deadliest cancers in the world. Increasing evidence suggests that circular RNAs (circRNAs) are implicated in CRC pathogenesis. This study aimed to determine the role of circAPLP2 and explore a potential mechanism of circAPLP2 action in CRC. Methods The expression of circAPLP2, miR-335-5p and helicase lymphoid-specific (HELLS) mRNA in CRC tissues and cells was measured by quantitative real-time polymerase chain reaction (qPCR). The functional effects of circAPLP2 on cell cycle progression/cell apoptosis, colony formation, cell migration, invasion and glycolysis metabolism were investigated by flow cytometry assay, colony formation assay, wound healing assay, transwell assay and glycolysis stress test. Glycolysis metabolism was also assessed by the levels of glucose uptake and lactate production. The protein levels of HELLS and HK2 were detected by western blot. The interaction between circAPLP2 and miR-335-5p, or miR-335-5p and HELLS was verified by dual-luciferase reporter assay. The role of circAPLP2 on solid tumor growth in nude mice was investigated. Results circAPLP2 and HELLS were overexpressed, but miR-335-5p was downregulated in CRC tissues and cells. Functional analyses showed that circAPLP2 knockdown suppressed CRC cell cycle progression, colony formation, migration, invasion and glycolysis metabolism, induced cell apoptosis and blocked solid tumor growth in nude mice. Moreover, miR-335-5p was a target of circAPLP2, and miR-335-5p could also bind to HELLS. Rescue experiments presented that miR-335-5p inhibition reversed the effects of circAPLP2 knockdown, and HELLS overexpression abolished the role of miR-335-5p restoration. Importantly, circAPLP2 could positively regulate HELLS expression by mediating miR-335-5p. Conclusion circAPLP2 triggered CRC malignant development by increasing HELLS expression via targeting miR-335-5p, which might be a novel strategy to understand and treat CRC.

Download Full-text

The Role of Hydrogen Peroxide and Peroxiredoxins throughout the Cell Cycle

Antioxidants ◽

10.3390/antiox9040280 ◽

2020 ◽

Vol 9 (4) ◽

pp. 280 ◽

Cited By ~ 3

Author(s):

Sukyeong Heo ◽

Suree Kim ◽

Dongmin Kang

Keyword(s):

Cell Cycle ◽

Hydrogen Peroxide ◽

Peroxidase Activity ◽

Cell Cycle Progression ◽

Effector Proteins ◽

Cellular Damage ◽

Cycle Progression ◽

Cycle Dependent ◽

Regulation Of Cell Cycle

Hydrogen peroxide (H2O2) is an oxidizing agent that induces cellular damage at inappropriate concentrations and gives rise to an arrest during cell cycle progression, causing cell death. Recent evidence indicates that H2O2 also acts as a promoter for cell cycle progression by oxidizing specific thiol proteins. The intracellular concentration of H2O2 is regulated tightly, enabling its use as a cellular signaling molecule while minimizing its potential to cause cellular damage. Peroxiredoxins (Prxs) have peroxidase activity toward H2O2, organic hydroperoxides, and peroxynitrite for protecting cells from oxidative stress. They are suggested to work as signaling mediators, allowing the local accumulation of H2O2 by inactivating their peroxidase activity uniquely compared with other antioxidant proteins such as catalase and glutathione peroxidase. Given that Prxs are highly sensitive to oxidation by H2O2, they act as sensors and transducers of H2O2 signaling via transferring their oxidation state to effector proteins. The concentrations of intracellular H2O2 increase as the cell cycle progresses from G1 to mitosis. Here, we summarize the roles of Prxs with regard to the regulation of cell cycle-dependent kinase activity and anaphase-promoting complex/cyclosome in terms of changes in H2O2 levels. Protection of the cell from unwanted progression of the cell cycle is suggested to be a role of Prx. We discuss the possible roles of Prxs to control H2O2 levels.

Download Full-text

Epigenetic Regulation by lncRNAs: An Overview Focused on UCA1 in Colorectal Cancer

Cancers ◽

10.3390/cancers10110440 ◽

2018 ◽

Vol 10 (11) ◽

pp. 440 ◽

Cited By ~ 15

Author(s):

Bernadette Neve ◽

Nicolas Jonckheere ◽

Audrey Vincent ◽

Isabelle Van Seuningen

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Cell Cycle Progression ◽

Cycle Progression ◽

Regulate Gene Expression ◽

Metastatic Lesions ◽

Colorectal Cancer Cells ◽

Regulation Of Cell Cycle ◽

Integrate Research

Colorectal cancers have become the second leading cause of cancer-related deaths. In particular, acquired chemoresistance and metastatic lesions occurring in colorectal cancer are a major challenge for chemotherapy treatment. Accumulating evidence shows that long non-coding (lncRNAs) are involved in the initiation, progression, and metastasis of cancer. We here discuss the epigenetic mechanisms through which lncRNAs regulate gene expression in cancer cells. In the second part of this review, we focus on the role of lncRNA Urothelial Cancer Associated 1 (UCA1) to integrate research in different types of cancer in order to decipher its putative function and mechanism of regulation in colorectal cancer cells. UCA1 is highly expressed in cancer cells and mediates transcriptional regulation on an epigenetic level through the interaction with chromatin modifiers, by direct regulation via chromatin looping and/or by sponging the action of a diversity of miRNAs. Furthermore, we discuss the role of UCA1 in the regulation of cell cycle progression and its relation to chemoresistance in colorectal cancer cells.

Download Full-text

Differential Regulation of Cell Cycle Progression in Human Breast Cancer Cell Lines by the Estrogen Receptor

10.21236/ada394036 ◽

2000 ◽

Author(s):

James Direnzo ◽

Myles Brown

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Human Breast Cancer ◽

Cell Cycle Progression ◽

Differential Regulation ◽

Human Breast Cancer Cell ◽

Breast Cancer Cell Lines ◽

Human Breast ◽

Cycle Progression ◽

Regulation Of Cell Cycle

Download Full-text

LMNB2 promotes the progression of colorectal cancer by silencing p21 expression

Cell Death and Disease ◽

10.1038/s41419-021-03602-1 ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Chen-Hua Dong ◽

Tao Jiang ◽

Hang Yin ◽

Hu Song ◽

Yi Zhang ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Cycle ◽

Cell Proliferation ◽

Cell Cycle Progression ◽

Molecular Mechanisms ◽

Gene Set Enrichment Analysis ◽

Molecular Therapy ◽

Cycle Progression ◽

Cancer Tissues

AbstractColorectal cancer is the second common cause of death worldwide. Lamin B2 (LMNB2) is involved in chromatin remodeling and the rupture and reorganization of nuclear membrane during mitosis, which is necessary for eukaryotic cell proliferation. However, the role of LMNB2 in colorectal cancer (CRC) is poorly understood. This study explored the biological functions of LMNB2 in the progression of colorectal cancer and explored the possible molecular mechanisms. We found that LMNB2 was significantly upregulated in primary colorectal cancer tissues and cell lines, compared with paired non-cancerous tissues and normal colorectal epithelium. The high expression of LMNB2 in colorectal cancer tissues is significantly related to the clinicopathological characteristics of the patients and the shorter overall and disease-free cumulative survival. Functional analysis, including CCK8 cell proliferation test, EdU proliferation test, colony formation analysis, nude mouse xenograft, cell cycle, and apoptosis analysis showed that LMNB2 significantly promotes cell proliferation by promoting cell cycle progression in vivo and in vitro. In addition, gene set enrichment analysis, luciferase report analysis, and CHIP analysis showed that LMNB2 promotes cell proliferation by regulating the p21 promoter, whereas LMNB2 has no effect on cell apoptosis. In summary, these findings not only indicate that LMNB2 promotes the proliferation of colorectal cancer by regulating p21-mediated cell cycle progression, but also suggest the potential value of LMNB2 as a clinical prognostic marker and molecular therapy target.

Download Full-text