Prominent roles of ribosomal S6 kinase 4 (RSK4) in cancer

Xu, Junpeng; Jia, Qingge; Zhang, Yan; Yuan, Yuan; Xu, Tianqi; Yu, Kangjie; Chai, Jia; Wang, Kaijing; Chen, Ligang; Xiao, Tian; Li, Mingyang

doi:10.1016/j.prp.2021.153374

Cited by 18 publications

(13 citation statements)

References 86 publications

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“…RSK has important roles in the survival, growth, translation, and cell cycle of tumor cells ( Casalvieri et al, 2017 ). Abnormal expression of RSK has a close relationship with several tumor types, including TNBC ( Zhao et al, 2016 ; Yoon et al, 2021 ), colorectal cancer ( Xu J. et al, 2021 ), and lung cancer ( Poomakkoth et al, 2016 ; Casalvieri et al, 2017 ). To predict the cytotoxicity of compound 1 , molecular docking on RSK protein was undertaken.…”

Section: Resultsmentioning

confidence: 99%

Cytotoxicity and molecular-docking approach of a new rosane-type diterpenoid from the roots of Euphorbia nematocypha

et al. 2022

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A new rosane-type diterpenoid (1) along with nine known diterpenoids (2–10), were isolated from the dried roots of Euphorbia nematocypha. The absolute configuration was elucidated from spectroscopic (nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, and electronic circular dichroism) and optical-rotation analyses. Cytotoxicity and the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl radicals were determined. Compound 1 showed remarkable cytotoxicity against human cancer cell lines (HeLa, CT26, and HCC 1806) in vitro. The interaction between compound 1 and proteins of ribosomal S6 kinase was revealed using molecular docking and provided valuable insights into the cytotoxic mechanism of action of compound 1. The latter could be developed as a pharmaceutical agent in the future.

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Section: Resultsmentioning

confidence: 99%

Cytotoxicity and molecular-docking approach of a new rosane-type diterpenoid from the roots of Euphorbia nematocypha

et al. 2022

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“…With respect to ciliary function, besides SBF1, our model also identified DNAI4 and DNAAF5, both of which are dyneins associated with primary cilia. Finally, RPS6KA6 (also known as RSK4), another top-7 variable, is a known driver of oncogenesis in a variety of tumor types [83] , and has been associated with chemotherapy resistance in breast cancer [84] .…”

Section: Discussionmentioning

confidence: 99%

Random survival forest model identifies novel biomarkers of event-free survival in high-risk pediatric acute lymphoblastic leukemia

Bohannan

Coffman

Mitrofanova

2022

Computational and Structural Biotechnology Journal

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“…In this study, we developed a PTEN mutation-associated signature that included seven genes (GDPD2, GRB7, KCNK9, MUC3A, MYT1, RPS6KA6, and TSPYL5) that were selected by LASSO-Cox analysis, and by reviewing previous studies, we found that RPS6KA6 and TSPYL5 had been reported to be associated with the occurrence and development of EC. Ribosomal S6 kinase 4 (RSK4) is a tumor suppressor gene product (also known as RPS6KA6) that has been shown to be significantly downregulated in multiple malignancies—including those of the breast, colon, kidney, ovarian, and acute myeloid leukemia [ 20 – 27 ]; and it can inhibit tumor cell proliferation, invasion, and the epithelial mesenchymal transformation [ 28 , 29 ]. One study [ 30 ] showed that hypermethylation of RSK4 in EC resulted in a lowered expression level of RSK4 in EC relative to normal endometrial tissues and that reduced RSK4 methylation was associated with higher EC grade.…”

Section: Discussionmentioning

confidence: 99%

Significance of a PTEN Mutational Status-Associated Gene Signature in the Progression and Prognosis of Endometrial Carcinoma

Wang

Liu

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. PTEN mutations have been reported to be involved in the development and prognosis of endometrial carcinoma (EC). However, a prognostic gene signature associated with PTEN mutational status has not yet been developed. In this study, we generated a PTEN mutation-associated prognostic gene signature for EC. Methods. We obtained the single-nucleotide variation and transcriptomic profiling data from The Cancer Genome Atlas database as training data and implemented the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm to establish a PTEN mutation-associated prognostic gene signature. The overall survival rates of the high-risk and low-risk groups were determined with the Kaplan-Meier (K-M) method, and the accuracy of risk score prediction was tested by using the receiver operating characteristic (ROC) curve. Results. The K-M curves revealed that the EC patients with PTEN mutations augured favorable survival outcomes. Differential expression analysis between the EC patients with PTEN mutation and wild-type PTEN identified 224 differentially expressed genes (DEGs). Eighty-four DEGs that manifested prognostic value were fitted into the LASSO-Cox analysis, and a PTEN gene signature with seven mutation-associated prognostic genes that showed robust prognostic ability was constructed; this signature was then successfully validated in the other two datasets from the cBioPortal database as well as with 60 clinical specimens. Furthermore, the PTEN mutation-associated prognostic gene signature proved to be an independent prognostic predictor of EC. Remarkably, the EC patients in the high-risk group were characterized by higher tumor stages and grades as well as lower tumor mutation burden with respect to EC, with a poor survival outcome. Collectively, the PTEN mutation-associated prognostic gene signature that we developed could now be used as a favorable prognostic biomarker for EC. Conclusion. In summary, we developed and validated a prognostic predictor for EC associated with PTEN mutational status that may be used as a favorable prognostic biomarker and therapeutic target for EC.

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Prominent roles of ribosomal S6 kinase 4 (RSK4) in cancer

Cited by 18 publications

References 86 publications

Cytotoxicity and molecular-docking approach of a new rosane-type diterpenoid from the roots of Euphorbia nematocypha

Cytotoxicity and molecular-docking approach of a new rosane-type diterpenoid from the roots of Euphorbia nematocypha

Random survival forest model identifies novel biomarkers of event-free survival in high-risk pediatric acute lymphoblastic leukemia

Significance of a PTEN Mutational Status-Associated Gene Signature in the Progression and Prognosis of Endometrial Carcinoma

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