scholarly journals CSNK2B contributes to colorectal cancer cell proliferation by activating the mTOR signaling

2021 ◽  
Author(s):  
Shijun Yu ◽  
Qingqing Hu ◽  
Kailing Fan ◽  
Chen Yang ◽  
Yong Gao
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cancer Cell Proliferation ◽  
Gene Expression Microarray ◽  
Western Blots ◽  
Normal Tissues ◽  
Immunohistochemistry Analysis ◽  
Gene Expression Microarray Data

AbstractThe function of Casein kinase 2 beta (CSNK2B) in human malignancies has drawn increasing attention in recent years. However, its role in colorectal cancer (CRC) remains unclear. In the present study, we aimed to explore the expression and biological functions of CSNK2B in CRC. Public gene expression microarray data from online database and immunohistochemistry analysis demonstrated that CSNK2B was highly expressed in CRC tissues than in normal tissues. In vitro and in vivo cellular functional experiments showed that increased CSNK2B expression promoted CRC cell viability and tumorigenesis of CRC. Further western blots and rescue experiments confirmed that CSNK2B promoted CRC cell proliferation mainly by activating the mTOR signaling pathway. These findings identified CSNK2B as a novel oncogene contributing to the development of CRC.

scholarly journals DPP3/CDK1 contributes to the progression of colorectal cancer through regulating cell proliferation, cell apoptosis, and cell migration

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Yixin Tong ◽  
Yuan Huang ◽  
Yuchao Zhang ◽  
Xiangtai Zeng ◽  
Mei Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Apoptosis ◽  
Downstream Target ◽  
Normal Tissues ◽  
Physiological Processes ◽  
Mutual Regulation

AbstractAt present, colorectal cancer (CRC) has become a serious threat to human health in the world. Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent hydrolase that may be involved in several physiological processes. However, whether DPP3 affects the development and progression of CRC remains a mystery. This study is the first to demonstrate the role of DPP3 in CRC. Firstly, the results of immunohistochemistry analysis showed the upregulation of DPP3 in CRC tissues compared with normal tissues, which is statistically analyzed to be positively correlated with lymphatic metastasis, pathological stage, positive number of lymph nodes. Moreover, the high expression of DPP3 predicts poor prognosis in CRC patients. In addition, the results of cell dysfunction experiments clarified that the downregulation of DPP3 significantly inhibited cell proliferation, colony formation, cell migration, and promoted apoptosis in vitro. DPP3 depletion could induce cell apoptosis by upregulating the expression of BID, BIM, Caspase3, Caspase8, HSP60, p21, p27, p53, and SMAC. In addition, downregulation of DPP3 can reduce tumorigenicity of CRC cells in vivo. Furthermore, CDK1 is determined to be a downstream target of DPP3-mediated regulation of CRC by RNA-seq, qPCR, and WB. The interaction between DPP3 and CDK1 shows mutual regulation. Specifically, downregulation of DPP3 can accentuate the effects of CDK1 knockdown on the function of CRC cells. Overexpression of CDK1 alleviates the inhibitory effects of DPP3 knockdown in CRC cells. In summary, DPP3 has oncogene-like functions in the development and progression of CRC by targeting CDK1, which may be an effective molecular target for the prognosis and treatment of CRC.

scholarly journals hsa_circ_0000231 Promotes Colorectal Cancer Cell Growth Through Upregulation of CCND2 by IGF2BP3/miR-375 Dual Pathway

2020 ◽  
Author(s):  
Wei Zhang ◽  
Bo Wang ◽  
Yang Yang ◽  
Zhen Zhang ◽  
Quan Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
In Situ Hybridization ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Cancer Cell Growth ◽  
Normal Tissues

Abstract Background circular RNAs (circRNAs) recently have been emerged as vital regulators for involvement of initiation and progression of diverse kinds of human cancers. This study aimed to investigate the role of circRNAs in colorectal cancer (CRC). Methods The expression profile of circRNAs in 5 pairs of CRC tissues and adjacent normal tissues were analyzed by Microarray. Quantitative real-time PCR and in situ hybridization and Base Scope Assay were used to determine the level and prognostic values of hsa_circ_0000231. Then, functional experiments in vitro and in vivo were performed to investigate the effects of hsa_circ_0000231 on cell proliferation. Mechanistically, fluorescent in situ hybridization, dual luciferase reporter assay, RNA pull-down and RNA immunoprecipitation experiments were performed to confirm the interaction between hsa_circ_0000231 and IGF2BP3 or has_miR-375. Results hsa_circ_0000231 was evidently up-regulated in CRC primary tissues, which was indicated to poor prognosis of CRC patients. The results demonstrated that hsa_circ_0000231 could promote CRC cell proliferation as well as tumorigenesis in vitro and in vivo. Mechanistic analysis showed that hsa_circ_0000231 might on the one hand act as a ceRNA (competing endogenous RNA) of miR-375 to regulate cyclin D2 (CCND2), and on the other hand bind to IGF2BP3 protein to protect CCND2 from being degraded. Conclusion Our findings suggest that hsa_circ_0000231 facilitated CRC progression by sponging miR-375 or binding to IGF2BP3 to modulate CCND2. This discovery implied that has_circ_0000231 may be a potential new diagnostic and therapeutic biomarker for CRC.

hsa_circ_0000231 promotes colorectal cancer cell growth through upregulation of CCND2 by IGF2BP3/miR-375 dual pathway 

2020 ◽  
Author(s):  
Wei Zhang ◽  
Bo Wang ◽  
Yang Yang ◽  
Zhen Zhang ◽  
Quan Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Expression Profiles ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Cancer Cell Growth ◽  
Normal Tissues

Abstract Background and aim Circular RNAs (circRNAs) have emerged as vital regulators of the initiation and progression of diverse kinds of human cancers. This study aimed to investigate the role of circRNAs in colorectal cancer (CRC). Methods The expression profiles of circRNAs in five pairs of CRC tissues and adjacent normal tissues were analyzed using microarray. Quantitative real-time polymerase chain reaction, in situ hybridization, and BaseScope Assay were used to determine the level and prognostic values of hsa_circ_0000231. Then, in vitro and in vivo functional experiments were performed to investigate the effects of hsa_circ_0000231 on cell proliferation. Mechanistically, fluorescence in situ hybridization, dual-luciferase reporter assay, and RNA pull-down and RNA immunoprecipitation experiments were performed to confirm the interaction between hsa_circ_0000231 and Insulin-like growth factor 2 mRNA-binding protein 3(IGF2BP3) or has_miR-375. Results The expression of hsa_circ_0000231 was upregulated in CRC primary tissues, which indicated poor prognosis of patients with CRC. The results demonstrated that hsa_circ_0000231 could promote CRC cell proliferation as well as tumorigenesis in vitro and in vivo. The mechanistic analysis showed that hsa_circ_0000231 might, on the one hand, act as a competing endogenous RNA of miR-375 to promote cyclin D2 (CCND2) and, on the other hand, bind to the IGF2BP3 protein to prevent CCND2 degradation. Conclusion The findings suggested that hsa_circ_0000231 facilitated CRC progression by sponging miR-375 or binding to IGF2BP3 to modulate CCND2, implying that has_circ_0000231 might be a potential new diagnostic and therapeutic biomarker of CRC.

scholarly journals miR-375-NAT10 Axis Dysfunction Promotes Oral Cancer Development and Mediates Cdk7 Stabilizing and Cell Cycle Progression

2021 ◽  
Author(s):  
Chen ZOU ◽  
Xia LI ◽  
Haigang WEI ◽  
Siyuan WU ◽  
Jing SONG ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Oral Cancer ◽  
Cancer Cell ◽  
In Vivo Studies ◽  
Cancer Tissue ◽  
Cancer Cell Proliferation ◽  
Western Blots

Abstract Background: Oral cancer is the most common cancer with poor prognosis and outcome for the patients due to the challenging diagnosis and limited treatment possibilities. However, the molecular underpinnings behind the malignant progression of oral cancer remain incompletely understood. Methods: The expression profiling of NAT10 and CDK7 in oral cancer patients were assessed by IHC, qPCR and western blots. ShRNA was used to silence gene expression. The biological function of NAT10 and CDK7 in cholangiocarcinoma was investigated using in vitro and in vivo studies including, transwell cell migration, plate cloning, CCK8, shRNA interference, western blots, flow cytometry and xenograft mouse model. The underlying molecular mechanism was determined by western blots and immunoprecipitation.Results: In this study, we demonstrated that deregulation of miR-375-NAT10 axis is among the most causes in inducing the acquisition of a tumorigenesis phenotype in oral cancer cells. NAT10 is abundant in oral cancer tissue. and its protein level is positively correlated with poor overall survival. Increased the level of NAT10 promotes oral cancer cell proliferation in vitro as well as xenograft tumorigenicity in vivo. Most importantly, NAT10 regulates cancer cell proliferation through stabilizing CDK7 thus regulating the cell cycle. NAT10 as an acetyltransferase is responsible for CDK7 acetylation at lysine 328 (K328Ac). Moreover, it was found that the expression of miR-375 is abnormally alleviated in oral cancer tissues. Bioinformatics analysis revealed a targeted complementary binding site between miR-375 and NAT10. Decreased expression of miR-375 promotes expression of NAT10.Conclusion: Our study showed that NAT10 plays a strong carcinogenic role in oral cancer tumorigenesis by acetylating CDK7 at K382 thus promotion stability. Moreover, NAT10 may serve as a target for miR-375. Therefore, targeting NAT10 may provide a new and effective therapeutic strategy to inhibit the tumorigenicity of oral cancer.

scholarly journals hsa_circ_0000231 promotes colorectal cancer cell growth through upregulation of CCND2 by IGF2BP3/miR-375 dual pathway

2020 ◽  
Author(s):  
Wei Zhang ◽  
Bo Wang ◽  
Yang Yang ◽  
Zhen Zhang ◽  
Quan Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Expression Profiles ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Cancer Cell Growth ◽  
Normal Tissues

Abstract Background and aim Circular RNAs (circRNAs) have emerged as vital regulators of the initiation and progression of diverse kinds of human cancers. This study aimed to investigate the role of circRNAs in colorectal cancer (CRC).Methods The expression profiles of circRNAs in five pairs of CRC tissues and adjacent normal tissues were analyzed using microarray. Quantitative real-time polymerase chain reaction, in situ hybridization, and BaseScope Assay were used to determine the level and prognostic values of hsa_circ_0000231. Then, in vitro and in vivo functional experiments were performed to investigate the effects of hsa_circ_0000231 on cell proliferation. Mechanistically, fluorescence in situ hybridization, dual-luciferase reporter assay, and RNA pull-down and RNA immunoprecipitation experiments were performed to confirm the interaction between hsa_circ_0000231 and Insulin-like growth factor 2 mRNA-binding protein 3(IGF2BP3) or has_miR-375. Results The expression of hsa_circ_0000231 was upregulated in CRC primary tissues, which indicated poor prognosis of patients with CRC. The results demonstrated that hsa_circ_0000231 could promote CRC cell proliferation as well as tumorigenesis in vitro and in vivo. The mechanistic analysis showed that hsa_circ_0000231 might, on the one hand, act as a competing endogenous RNA of miR-375 to promote cyclin D2 (CCND2) and, on the other hand, bind to the IGF2BP3 protein to prevent CCND2 degradation. Conclusion The findings suggested that hsa_circ_0000231 facilitated CRC progression by sponging miR-375 or binding to IGF2BP3 to modulate CCND2, implying that has_circ_0000231 might be a potential new diagnostic and therapeutic biomarker of CRC.

scholarly journals Sevoflurane inhibits malignant progression of colorectal cancer via hsa_circ_0000231-mediated miR-622

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Jingpeng Wang ◽  
Shuyuan Li ◽  
Gaofeng Zhang ◽  
Huihua Han
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Volatile Anesthetic ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas

Abstract Background Sevoflurane (Sev), a commonly used volatile anesthetic, has been reported to inhibit the process of colorectal cancer (CRC). Circular RNAs (circRNAs) are revealed to participate in the pathogenesis of CRC. This study aims to reveal the mechanism of hsa_circ_0000231 in Sev-mediated CRC progression. Methods The expression of hsa_circ_0000231 and microRNA-622 (miR-622) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein level was determined by western blot analysis. Cell proliferation was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cell colony formation and DNA content quantitation assays. Cell apoptosis was detected by Annexin V-fluorescein isothiocyanate and propidium iodide double staining and caspase 3 activity assays. Cell migration and invasion were investigated by wound-healing and transwell invasion assays, respectively. The putative relationship between hsa_circ_0000231 and miR-622 was predicted by circular RNA Interactome online database, and identified by dual-luciferase reporter and RNA immunoprecipitation assays. The impacts of hsa_circ_0000231 on Sev-mediated tumor formation in vivo were presented by in vivo assay. Results Hsa_circ_0000231 expression was upregulated, while miR-622 was downregulated in CRC tissues and cells compared with control groups. Sev treatment decreased hsa_circ_0000231 expression, but increased miR-622 expression in CRC cells. Sev treatment suppressed cell proliferation, migration and invasion, and induced cell apoptosis. Hsa_circ_0000231 overexpression restored Sev-mediated CRC progression in vitro. Additionally, hsa_circ_0000231 acted as a sponge of miR-622, and miR-622 inhibitors reversed the impacts of hsa_circ_0000231 silencing on CRC process. Furthermore, Sev treatment inhibited tumor growth by regulating hsa_circ_0000231 in vivo. Conclusion Hsa_circ_0000231 attenuated Sev-aroused repression impacts on CRC development by sponging miR-622. This findings may provide an appropriate anesthetic protocol for CRC sufferers undergoing surgery.

scholarly journals PRMT1-mediated EZH2 methylation promotes breast cancer cell proliferation and tumorigenesis

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Zhongwei Li ◽  
Diandian Wang ◽  
Xintian Chen ◽  
Wenwen Wang ◽  
Pengfei Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Cycle Progression ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Ezh2 Expression

AbstractProtein arginine methyltransferase 1 (PRMT1) is able to promote breast cancer cell proliferation. However, the detailed mechanisms of PRMT1-mediated breast cancer cell proliferation are largely unknown. In this study, we reveal that PRMT1-mediated methylation of EZH2 at the R342 site (meR342-EZH2) has a great effect on PRMT1-induced cell proliferation. We also demonstrate that meR342-EZH2 can accelerate breast cancer cell proliferation in vitro and in vivo. Further, we show that meR342-EZH2 promotes cell cycle progression by repressing P16 and P21 transcription expression. In terms of mechanism, we illustrate that meR342-EZH2 facilitates EZH2 binding with SUZ12 and PRC2 assembly by preventing AMPKα1-mediated phosphorylation of pT311-EZH2, which results in suppression of P16 and P21 transcription by enhancing EZH2 expression and H3K27me3 enrichment at P16 and P21 promoters. Finally, we validate that the expression of PRMT1 and meR342-EZH2 is negatively correlated with pT311-EZH2 expression. Our findings suggest that meR342-EZH2 may become a novel therapeutic target for the treatment of breast cancer.

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