The Immunological Role of CDK4/6 and Potential Mechanism Exploration in Ovarian Cancer

Liu, Chen; Huang, Yuhan; Cui, Yaoyuan; Zhou, Jun; Xu, Qian; Zhang, Li; Xi, Li; Li, Yuan; Guo, Ensong; Yang, Bin; Li, Xi; Fan, Junpeng; Fu, Yu; Liu, Si; Hu, Dianxing; Xiao, Rourou; Wang, Zizhuo; Dou, Yingyu; Wang, Wei; Li, Wenting; Yang, Xiaohang; Liu, Jingbo; Peng, Weiming; Qin, Tianyu; You, Lixin; Lü, Fang; Sun, Chaoyang

doi:10.3389/fimmu.2021.799171

Cited by 10 publications

(10 citation statements)

References 33 publications

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“…At present, although the research on gastric cancer has achieved great success, the molecular mechanism of gastric cancer is still not fully understood, and the effective treatment of gastric cancer is still a hot issue [ 2 , 3 ]. Abnormal expression of CDK6 affects the initiation and progression of various malignant tumors [ 4 ]. One of the hallmarks of cancer is cell cycle disorder that leads to abnormal cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

Expression of CDK6 in Stomach Cancer and the Effect of CDK4/6 Inhibitor PD-0332991 on the Function of Stomach Cancer Cells

Liu

Zhao

Han

et al. 2022

Computational and Mathematical Methods in Medicine

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Objective. To study the expression and prognostic value of CDK6 in stomach cancer and the function of CDK4/6 inhibitor PD-0332991 on the proliferation of stomach cancer cells. Methods. Immunohistochemistry was used to detect the expression of CDK6 in stomach cancer tissues and adjacent normal tissues and to analyze the effect of CDK6 on clinicopathological parameters of stomach cancer patients. Kaplan-Meier plotter was employed to study the relationship between CDK6 and overall survival in stomach cancer. Western blot and RT-PCR were used to detect protein and gene expression of CDK6 in different cells. The effects of CDK4/6 inhibitor PD-0332991 on apoptosis and aging of stomach cancer cells were detected by flow cytometry and β-galactosidase aging staining assay. The effects of CDK4/6 inhibitor PD-0332991 on the invasion and migration of stomach cancer cells were explored by the wound healing experiment and the Transwell experiment. The supernatant of stomach cancer cells was collected, and the effect of CDK4/6 inhibitor PD-0332991 on tumor markers of stomach cancer cells was detected by biochemical immunoassay. Results. (1) CDK6 was highly expressed in stomach cancer tissues and cells. (2) Abnormally elevated CDK6 expression results in shorter survival in stomach cancer patients. (3) CDK4/6 inhibitor PD-0332991 could block the proliferation of stomach cancer cells, but not stomach epithelial proliferation. PD-0332991 could inhibit the secretion of pro-GRP by MGC 823. (4) PD-0332991 could advance the development of the apoptosis and senescence of stomach cancer cells and suppressed the invasion and migration of stomach cancer cells. Conclusion. CDK6 expression is elevated in gastric cancer, and the CDK4/6 inhibitor PD-0332991 can remarkably promote apoptosis and senescence of stomach cancer cells and effectively inhibit the migration and invasion of stomach cancer cells.

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Section: Introductionmentioning

confidence: 99%

Expression of CDK6 in Stomach Cancer and the Effect of CDK4/6 Inhibitor PD-0332991 on the Function of Stomach Cancer Cells

Liu

Zhao

Han

et al. 2022

Computational and Mathematical Methods in Medicine

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“…AC020907.2 is positively related to overall survival in glioma [ 34 ]. Correlation analysis between AC026461.1 and has-miR-330-5p has been found in ovarian cancer [ 35 ]. HOXC10 is implicated in luminal breast cancer [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Crucial lncRNAs for Luminal A Breast Cancer through RNA Sequencing

Jia

Lei

Jiang

et al. 2022

International Journal of Endocrinology

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Background. The growing body of evidence indicates aberrant expression of long noncoding RNAs (lncRNAs) in breast cancer. Nevertheless, a few studies have focused on identifying key lncRNAs for patients with luminal A breast cancer. In our study, we tried to find key lncRNAs and mRNAs in luminal A breast cancer. Methods. RNA sequencing was performed to identify differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) in luminal A breast cancer. The protein-protein interaction (PPI), DElncRNA-DEmRNA coexpression, DElncRNA-nearby DEmRNA interaction networks, and functional annotation were performed to uncover the function of DEmRNAs. Online databases were used to validate the RNA sequencing result. The diagnostic value of candidate mRNAs was evaluated by receiver operating characteristic (ROC) curve analysis. Results. A total number of 1451 DEmRNAs and 272 DElncRNAs were identified. Several hub proteins were identified in the PPI network, including TUBB3, HIST2H3C, MCM2, MYOC, NEK2, LIPE, FN1, FOXJ1, S100A7, and DLK1. In the DElncRNA-DEmRNA coexpression, some hub lncRNAs were identified, including AP001528.2, LINC00968, LINC02202, TRHDE-AS1, LINC01140, AL354707.1, AC097534.1, MIR222HG, and AL662844.4. The mRNA expression result of TFF1, COL10A1, LEP, PLIN1, PGM5-AS1, and TRHDE-AD1 in the GSE98793 was consistent with the RNA sequencing result. The protein expression results of TUBB3, MCM2, MYOC, FN1, S100A7, and TFF1 were consistent with the mRNA expression result COL10A1, LEP, PLIN1, PGM5-AS1, and TRHDE-AD1 were capable of discriminating luminal A breast cancer and normal controls. Four lncRNA-nearby and coexpressed mRNA pairs of HOXC-AS3-HOXC10, AC020907.2-FXYD1, AC026461.1-MT1X, and AC132217.1-IGF2 were identified. AMPK (involved LIPE and LEP) and PPAR (involved PLIN1) were two significantly enriched pathways in luminal A breast cancer. Conclusion. This study could be helpful in unraveling the pathogenesis and providing novel therapeutic strategies for luminal A breast cancer.

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“…Another study has shown up-regulation of CDK4/6 and pRb levels in HER2 + breast cancer samples [334]. In ovarian cancer samples, up-regulation of CDK6 has been associated with shorted OS and immunosuppressive state [319]. Moreover, in this type of cancer, up-regulation of a functional counterpart of CDK4/6, i.e.…”

Section: Investigations In Clinical Samplesmentioning

confidence: 96%

A review on the role of cyclin dependent kinases in cancers

et al. 2022

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The Cyclin-dependent kinase (CDK) class of serine/threonine kinases has crucial roles in the regulation of cell cycle transition and is mainly involved in the pathogenesis of cancers. The expression of CDKs is controlled by a complex regulatory network comprised of genetic and epigenetic mechanisms, which are dysregulated during the progression of cancer. The abnormal activation of CDKs results in uncontrolled cancer cell proliferation and the induction of cancer stem cell characteristics. The levels of CDKs can be utilized to predict the prognosis and treatment response of cancer patients, and further understanding of the function and underlying mechanisms of CDKs in human tumors would pave the way for future cancer therapies that effectively target CDKs. Defects in the regulation of cell cycle and mutations in the genes coding cell-cycle regulatory proteins lead to unrestrained proliferation of cells leading to formation of tumors. A number of treatment modalities have been designed to combat dysregulation of cell cycle through affecting expression or activity of CDKs. However, effective application of these methods in the clinical settings requires recognition of the role of CDKs in the progression of each type of cancer, their partners, their interactions with signaling pathways and the effects of suppression of these kinases on malignant features. Thus, we designed this literature search to summarize these findings at cellular level, as well as in vivo and clinical levels.

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The Immunological Role of CDK4/6 and Potential Mechanism Exploration in Ovarian Cancer

Cited by 10 publications

References 33 publications

Expression of CDK6 in Stomach Cancer and the Effect of CDK4/6 Inhibitor PD-0332991 on the Function of Stomach Cancer Cells

Expression of CDK6 in Stomach Cancer and the Effect of CDK4/6 Inhibitor PD-0332991 on the Function of Stomach Cancer Cells

Identification of Crucial lncRNAs for Luminal A Breast Cancer through RNA Sequencing

A review on the role of cyclin dependent kinases in cancers

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