The steady-state level of CDK4 protein is regulated by antagonistic actions between PAQR4 and SKP2 and involved in tumorigenesis

Wang, Lin; Zhang, Rui; You, Xu; Zhang, Huanhuan; Wei, Siying; Cheng, Tingting; Cao, Qianqian; Wang, Zhenzhen; Chen, Yan

doi:10.1093/jmcb/mjx028

Cited by 28 publications

(22 citation statements)

References 46 publications

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“…The activity of the kinase complex was restricted to G1‐S phase, which is controlled by the regulatory subunits of D‐type cyclins and the cyclin‐dependent kinase (CDK) inhibitor p16 (INK4a) . The deregulation of CDK4 expression is associated with several aspects of tumourigenesis, including cell cycle arrest, proliferation and abnormal apoptosis . The down‐regulation of cyclin D1 and CDK4 suppressed human colorectal cancer cell proliferation .…”

Section: Discussionmentioning

confidence: 99%

MiR‐34b‐3p represses cell proliferation, cell cycle progression and cell apoptosis in non‐small‐cell lung cancer (NSCLC) by targeting CDK4

Feng

et al. 2019

J Cellular Molecular Medi

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Lung cancer is the most common incident cancer, with a high mortality worldwide, and non‐small‐cell lung cancer (NSCLC) accounts for approximately 85% of cases. Numerous studies have shown that the aberrant expression of microRNAs (miRNAs) is associated with the development and progression of cancers. However, the clinical significance and biological roles of most miRNAs in NSCLC remain elusive. In this study, we identified a novel miRNA, miR‐34b‐3p, that suppressed NSCLC cell growth and investigated the underlying mechanism. miR‐34b‐3p was down‐regulated in both NSCLC tumour tissues and lung cancer cell lines (H1299 and A549). The overexpression of miR‐34b‐3p suppressed lung cancer cell (H1299 and A549) growth, including proliferation inhibition, cell cycle arrest and increased apoptosis. Furthermore, luciferase reporter assays confirmed that miR‐34b‐3p could bind to the cyclin‐dependent kinase 4 (CDK4) mRNA 3′‐untranslated region (3′‐UTR) to suppress the expression of CDK4 in NSCLC cells. H1299 and A549 cell proliferation inhibition is mediated by cell cycle arrest and apoptosis with CDK4 interference. Moreover, CDK4 overexpression effectively reversed miR‐34‐3p‐repressed NSCLC cell growth. In conclusion, our findings reveal that miR‐34b‐3p might function as a tumour suppressor in NSCLC by targeting CDK4 and that miR‐34b‐3p may, therefore, serve as a biomarker for the diagnosis and treatment of NSCLC.

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Section: Discussionmentioning

confidence: 99%

MiR‐34b‐3p represses cell proliferation, cell cycle progression and cell apoptosis in non‐small‐cell lung cancer (NSCLC) by targeting CDK4

Feng

et al. 2019

J Cellular Molecular Medi

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“…It is well known that abnormal expression of cancer-related genes is related to occurrence and development of a wide range of human malignancies 8–10. Progestin and adipoQ receptor 4 (PAQR4) is a member of the PAQR4 family 11,12. It is documented that the PAQR4 family plays an important role in a number of biological processes, including tumor development and metabolism 13–15.…”

Section: Introductionmentioning

confidence: 99%

<p>PAQR4 promotes cell proliferation and metastasis through the CDK4-pRB-E2F1 pathway in non-small-cell lung cancer</p>

Liu²

2019

OTT

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Background It is reported that progestin and adipoQ receptor 4 (PAQR4) has a tumorigenic effect on human breast cancer, but the role of PAQR4 in non-small-cell lung cancer (NSCLC) is unknown. The aim of this study was to investigate the role of PAQR4 in NSCLC. Methods Quantitative real-time PCR (qRT-PCR) and immunohistchemical (IHC) staining were used to analyze the expression of PAQR4 in HCC tissues and adjacent normal tissues. MTT, colony formation assay, flow cytometry (FCM), wound healing assays and transwell invasion assays were used to investigate the effects of PAQR4 on cell proliferation, colony formation, cell cycle, migration and invasion. Murine xenograft model assay was carried out to characterize the effects of PAQR4 knockdown on tumor growth in vivo. Results In this study, we found that the expression of PAQR4 was significantly upregulated in the NSCLC tissues of patients compared with that in the matched non-cancerous tissues. In addition, we found that PAQR4 was also significantly up-regulated in the NSCLC cell lines compared with normal human lung epithelial cells. Besides, we found that the over-expression of PAQR4 promoted promoted proliferation, colony formation, migration and invasion of the NSCLC cells, whereas the knockdown of PAQR4 inhibited proliferation, colony formation, migration and invasion of the NSCLC cells. Furthermore, mechanistic studies showed that the CDK4-pRB-E2F1 pathway was involved in NSCLC. Conclusion Hence, these results suggest that PAQR4 may be used as a new target in NSCLC therapy.

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“…PICALM interacting mitotic regulator (PIMREG) could promote breast cancer aggressiveness via sustaining nuclear factor (NF)-κB activation ( Jiang et al, 2019 ). Progestin and adipoQ receptor family member (PAQR) 4 has been found to compete with S-phase kinase-associated protein (SKP) 2 for binding to the same region in cyclin-dependent kinase (CDK) 4, thereby abrogating SKP2-mediated ubiquitination of CDK4 and contributing to tumorigenesis ( Wang et al, 2017 ). Growth arrest specific 2 like 2 (GAS2L2), also known as G2L2, was reported to be involved in mediating the cross talk between filamentous actin and microtubules ( Stroud et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Prognostic lncRNA, miRNA, and mRNA Signatures in Papillary Thyroid Carcinoma

Wang

Zhao

et al. 2020

Front. Genet.

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The current focus in the treatment of papillary thyroid carcinoma (PTC) is tumor progression. The aim of this study was to build RNA-based classifiers and develop a comprehensive model to provide progression-free interval (PFI) risk prediction for PTC. The RNAseq data, miRNAseq data, and clinical information of PTC were downloaded from The Cancer Genome Atlas database. Based on the differently expressed RNAs, the least absolute shrinkage and selection operator (LASSO) Cox regression model was utilized to build the RNA-based classifiers for PFI of the patients with PTC. A 6messenger RNA (mRNA)-based classifier, a 5-long non-coding RNA (lncRNA)-based classifier, and a 4-microRNA (miRNA)-based classifier were constructed to predict the PFI. Patients with high risk based on the constructed RNA-based classifiers had worse prognosis in Kaplan-Meier curve analysis with log-rank test. The areas under the curves of the first, third, and fifth years in the training and testing set were 0.83, 0.82, and 0.82 and 0.67, 0.72, and 0.73 for the 6-mRNA-based classifier, respectively; 0.75, 0.84, and 0.85 and 0.71, 0.67, and 0.71 for the 5-lncRNA-based classifier, respectively; and 0.70, 0.77, and 0.79 and 0.74, 0.67, and 0.66 for the 4-miRNA-based classifier, respectively. The prediction capability of the three RNA-based classifiers was superior to the TNM stage system. Furthermore, a nomogram based on the verified independent prognostic factors was established for the prognostic prediction. The C-index and calibration plots indicated good predictive accuracy of the nomogram. In summary, the 6-mRNA-based classifier and 5-lncRNA-based classifier constructed in this study were independent prognostic factors for PTC.

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The steady-state level of CDK4 protein is regulated by antagonistic actions between PAQR4 and SKP2 and involved in tumorigenesis

Cited by 28 publications

References 46 publications

MiR‐34b‐3p represses cell proliferation, cell cycle progression and cell apoptosis in non‐small‐cell lung cancer (NSCLC) by targeting CDK4

MiR‐34b‐3p represses cell proliferation, cell cycle progression and cell apoptosis in non‐small‐cell lung cancer (NSCLC) by targeting CDK4

<p>PAQR4 promotes cell proliferation and metastasis through the CDK4-pRB-E2F1 pathway in non-small-cell lung cancer</p>

Prognostic lncRNA, miRNA, and mRNA Signatures in Papillary Thyroid Carcinoma

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