Progesterone induces cell apoptosis via the CACNA2D3/Ca2+/p38 MAPK pathway in endometrial cancer

Kong, Xiangnan; Li, Min; Shao, Kai; Yang, Yinrong; Wang, Qian; Cai, Mei-Juan

doi:10.3892/or.2019.7396

Cited by 26 publications

(24 citation statements)

References 35 publications

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“…In the KEGG enrichment, CACNA2D3 and DUSP3 were taken part in the MAPK signaling pathway. CACNA2D3 (calcium voltage-gated channel auxiliary subunit alpha2delta3) plays an important role in canceration [ 64 – 66 ]. CACNA2D3 is expressed in low levels in endometrial cancer tissues and cells [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

Revealing potential diagnostic gene biomarkers of septic shock based on machine learning analysis

Fan

Qiu-feng

et al. 2022

BMC Infect Dis

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Background Sepsis is an inflammatory response caused by infection with pathogenic microorganisms. The body shock caused by it is called septic shock. In view of this, we aimed to identify potential diagnostic gene biomarkers of the disease. Material and methods Firstly, mRNAs expression data sets of septic shock were retrieved and downloaded from the GEO (Gene Expression Omnibus) database for differential expression analysis. Functional enrichment analysis was then used to identify the biological function of DEmRNAs (differentially expressed mRNAs). Machine learning analysis was used to determine the diagnostic gene biomarkers for septic shock. Thirdly, RT-PCR (real-time polymerase chain reaction) verification was performed. Lastly, GSE65682 data set was utilized to further perform diagnostic and prognostic analysis of identified superlative diagnostic gene biomarkers. Results A total of 843 DEmRNAs, including 458 up-regulated and 385 down-regulated DEmRNAs were obtained in septic shock. 15 superlative diagnostic gene biomarkers (such as RAB13, KIF1B, CLEC5A, FCER1A, CACNA2D3, DUSP3, HMGN3, MGST1 and ARHGEF18) for septic shock were identified by machine learning analysis. RF (random forests), SVM (support vector machine) and DT (decision tree) models were used to construct classification models. The accuracy of the DT, SVM and RF models were very high. Interestingly, the RF model had the highest accuracy. It is worth mentioning that ARHGEF18 and FCER1A were related to survival. CACNA2D3 and DUSP3 participated in MAPK signaling pathway to regulate septic shock. Conclusion Identified diagnostic gene biomarkers may be helpful in the diagnosis and therapy of patients with septic shock.

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Section: Discussionmentioning

confidence: 99%

Revealing potential diagnostic gene biomarkers of septic shock based on machine learning analysis

Fan

Qiu-feng

et al. 2022

BMC Infect Dis

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“…In non-classical pathway, PRE binds to proto-oncogene tyrosine-protein Src, mitogen activated protein kinase and protein kinase B, and then activates downstream effector targets wingless-type MMTV integration site family member 1, cyclin D1, epidermal growth factor receptor and transcription of p21. Progesterone exerts a tumour suppressive effect by inducing apoptosis via activation of the MAPK pathway ( 10 ). The apoptosis of CRC cells is due to the up-regulation of GADD45α and activation of MAPKs (JNK, p38 and ERK) ( 53 ).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, progesterone regulates various cancer cell phenotypes, including proliferation, apoptosis, angiogenesis and autophagy ( 9 ). Studies have suggested that progesterone promotes apoptosis and an inhibitory effect is observed on cell proliferation in endometrial cancer ( 10 , 11 ). Progesterone-induced apoptosis occurs by arresting the progression from the G 1 phase to S phase ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

Progesterone suppresses the progression of colonic carcinoma by increasing the activity of the GADD45α/JNK/c‑Jun signalling pathway

Zhang

Wen

Guo³

et al. 2021

Oncol Rep

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Colorectal cancer (CRC) is the third most diagnosed cancer worldwide. Progesterone is associated with a decreased risk of CRC and leads to a favourable prognosis. However, the specific mechanism by which progesterone suppresses malignant progression remains to be elucidated. In the present study, the level of progesterone was first analysed in 77 patients with CRC, and immunohistochemistry was performed to detect the expression of progesterone receptor (PGR) in the paired specimens. The correlations between progesterone, PGR and CRC prognosis were assessed. A Cell Counting Kit-8 assay was then used to detect proliferation of the CRC cells. Flow cytometry was performed to estimate apoptosis and to evaluate the cycle of the CRC cells. A xenograft tumour model was established in nude mice to assess the role of progesterone in tumour growth. Finally, a PCR microarray was used to screen differentially expressed genes to further interpret the mechanism by which progesterone inhibits the malignant progression of CRC. It was found that low expression of progesterone and PGR were significantly associated with poor prognosis of CRC. In addition, progesterone suppressed CRC cell proliferation by arresting the cell cycle and inducing apoptosis in vitro . Moreover, the inhibitory role of progesterone in tumour growth was verified in vivo . Further investigation showed that the level of growth arrest and DNA damage-inducible protein α (GADD45α) was up-regulated by progesterone, and this was followed by the activation of the JNK pathway. Progesterone increased the activity of the JNK pathway via GADD45α to inhibit proliferation by arresting the cell cycle and inducing apoptosis, thereby suppressing the malignant progression of CRC. Therefore, it can be concluded that progesterone and PGR might act as inhibiting factors for poor prognosis of CRC.

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“…Not surprisingly, the expression of PR is gradually lost with progression of EC, thus abrogating the tumor suppressive properties of progesterone. Several mechanisms elucidating PR mediated tumor suppressor have been proposed, including cell cycle arrest, inhibiting proliferation, and activating apoptosis ( 33 , 34 ). We demonstrated that PR could also act through upregulating KLF9, thus inhibiting the initiation and progression of EC.…”

Section: Discussionmentioning

confidence: 99%

Progesterone receptor inhibits the proliferation and invasion of endometrial cancer cells by up regulating Krüppel-like factor 9

Yan¹,

Zhang²,

Ke³

et al. 2020

Transl Cancer Res TCR

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Background Krüppel-like factor 9 (KLF9) is one of the most important members of the KLF family, and is abnormally expressed in many tumors. However, the detailed function of KLF9 in endometrial cancer (EC) was barely investigated. Methods In this study, a total of 52 paired EC tissues were recruited to detect the KLF9 expression. Then a serial of phenotypic experiments and mechanism researches were performed. Results The results showed that KLF9 expression was decreased in EC tissues, and the reduced expression of KLF9 is associated with highly metastatic capacity of EC cells. KLF9 could inhibit the proliferation and invasion of EC cells by inhibiting the Wnt/β-catenin signaling pathway. Progesterone receptor (PR) could bind to KLF9 promoter and a positive correlation between KLF9 and PR expression was witnessed. Conclusions Taken together, the reduction of KLF9 induced by PR might participate in the development of EC and targeting KLF9 may provide a novel strategy for EC management.

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Progesterone induces cell apoptosis via the CACNA2D3/Ca2+/p38 MAPK pathway in endometrial cancer

Cited by 26 publications

References 35 publications

Revealing potential diagnostic gene biomarkers of septic shock based on machine learning analysis

Revealing potential diagnostic gene biomarkers of septic shock based on machine learning analysis

Progesterone suppresses the progression of colonic carcinoma by increasing the activity of the GADD45α/JNK/c‑Jun signalling pathway

Progesterone receptor inhibits the proliferation and invasion of endometrial cancer cells by up regulating Krüppel-like factor 9

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