Epac1 is involved in cell cycle progression in lung cancer through PKC and Cx43 regulation

Sun, Qian; Wang, Dai; Ai, Ganghao; Tian, Longben; Zhao, Long; Chen, Renzhen; Wang, Kai; Guo, Dongbei; Yao, Youliang; Liu, Wenzhi; Kong, Xiangyu; Chen, Xiaoxuan; Zhang, Yongxing

doi:10.5603/fhc.a2018.0004

Cited by 2 publications

(2 citation statements)

References 28 publications

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“…Mammalian exchange protein directly activated by cAMP isoform 1 (EPAC1), encoded by RAPGEF3 gene, acts as guanine exchange factor for Ras-like Rap small GTPases [39]. EPAC1 expression was lower in lung cancer tissue compared to expression in normal specimens and associated with the degree malignancy and lymph-node metastasis [40]. SGK is one of three isoforms of the serum glucocorticoid regulated kinase family of serine/threonine kinases.…”

Section: Discussionmentioning

confidence: 99%

Analysis of genomic and transcriptomic variations as prognostic signature for lung adenocarcinoma

Zengin

Önal-Süzek

2020

BMC Bioinformatics

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Background Lung cancer is the leading cause of the largest number of deaths worldwide and lung adenocarcinoma is the most common form of lung cancer. In order to understand the molecular basis of lung adenocarcinoma, integrative analysis have been performed by using genomics, transcriptomics, epigenomics, proteomics and clinical data. Besides, molecular prognostic signatures have been generated for lung adenocarcinoma by using gene expression levels in tumor samples. However, we need signatures including different types of molecular data, even cohort or patient-based biomarkers which are the candidates of molecular targeting. Results We built an R pipeline to carry out an integrated meta-analysis of the genomic alterations including single-nucleotide variations and the copy number variations, transcriptomics variations through RNA-seq and clinical data of patients with lung adenocarcinoma in The Cancer Genome Atlas project. We integrated significant genes including single-nucleotide variations or the copy number variations, differentially expressed genes and those in active subnetworks to construct a prognosis signature. Cox proportional hazards model with Lasso penalty and LOOCV was used to identify best gene signature among different gene categories. We determined a 12-gene signature (BCHE, CCNA1, CYP24A1, DEPTOR, MASP2, MGLL, MYO1A, PODXL2, RAPGEF3, SGK2, TNNI2, ZBTB16) for prognostic risk prediction based on overall survival time of the patients with lung adenocarcinoma. The patients in both training and test data were clustered into high-risk and low-risk groups by using risk scores of the patients calculated based on selected gene signature. The overall survival probability of these risk groups was highly significantly different for both training and test datasets. Conclusions This 12-gene signature could predict the prognostic risk of the patients with lung adenocarcinoma in TCGA and they are potential predictors for the survival-based risk clustering of the patients with lung adenocarcinoma. These genes can be used to cluster patients based on molecular nature and the best candidates of drugs for the patient clusters can be proposed. These genes also have a high potential for targeted cancer therapy of patients with lung adenocarcinoma.

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Section: Discussionmentioning

confidence: 99%

Analysis of genomic and transcriptomic variations as prognostic signature for lung adenocarcinoma

Zengin

Önal-Süzek

2020

BMC Bioinformatics

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“…[16] CX43 , as a member of CX family, was alleviated in a few of solid tumors, including breast cancer, [17] ovarian cancer, [18] and lung cancer. [19] In our previous study, we found that CX43 was highly expressed in BC tissues. [5,20] Once again, we verified that CX43 might be a potential target for BC treatment.…”

Section: Discussionmentioning

confidence: 99%

Tumor-suppressor microRNA-139-5p restrains bladder cancer cell line ECV-304 properties via targeting Connexin 43

Chi

Wang

et al. 2019

Chinese Medical Journal

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Background:In our previous paper, we demonstrated that Connexin 43 (CX43) was highly expressed in bladder cancer (BC) tissues. But the molecular mechanism about microRNAs (miRNAs) regulation upstream of CX43 in BC has not been well elucidated and remains to be further studied. MicroRNA-139-5p (miR-139-5p) is a tumor suppressor in progression of multifarious cancers including BC. Nevertheless, the underlying mechanisms of CX43/miR-139-5p in tumorigenesis of BC are still not well illustrated. The specific objective of our study was to inquiry the effect of CX43/miR-139-5p on BC progression and its underlying mechanism.Methods:The bioinformatics analysis softwares were applied to predict the miRNAs in the upstream of CX43. First, the expression levels of miR-139-5p in BC tissues (tumor) and paracancer tissues (normal) were investigated using the data from The Cancer Genome Atlas database. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression level of miR-139-5p in three human BC cell lines 5637, T24, ECV-304 and a human bladder epithelial immortalized cell line SV-HUC-1 (normal control). Then si-CX43, si-control, miR-139-5p mimic, and its negative control (NC) were transfected into BC cell line ECV-304. The relationship of miR-139-5p and CX43 was analyzed by dual-luciferase reporter assay. The qRT-PCR and Western blotting were used to test the mRNA and protein expression level of CX43. The proliferation of ECV-304 and T24 cells were examined by cell counting kit-8. The migration and invasion of ECV-304 cells were tested by transwell assay. To determine whether miR-139-5p would affect cell proliferation, migration and invasion by targeting CX43, we executed the rescue assay. The comparison between two groups was analyzed by Student's t test, and comparisons among multiple samples were performed by one-way analysis of variance and a Bonferroni post hoc test.Results:The expression of miR-139-5p was remarkably down-regulated in BC tissues (tumor vs. normal, 2.286 ± 0.017 vs. 3.211 ± 0.034, t = 11.540, P < 0.0001) and cell lines (P < 0.01 in all BC cell lines). Besides, we also indicated that over-expression of miR-139-5p reduced the proliferation of ECV-304 (P = 0.001) and T24 cells (P = 0.005). Moreover, miR-139-5p over-expression weakened the invasion (P = 0.001) and migration (P = 0.001) of ECV-304 cells. Furthermore, the relative luciferase activity of CX43-wild type construct was distinctly lessened by up-regulation of miR-139-5p (miR-139-5p mimic NC vs. miR-139-5p mimic, 0.916 ± 0.063 vs. 0.356 ± 0.048, t = 7.085, P = 0.002), nevertheless the activity of CX43-mutant type construct was untouched (miR-139-5p mimic NC vs. miR-139-5p mimic, 0.918 ± 0.057 vs. 0.878 ± 0.039, t = 0.577, P = 0.595). Finally, the rescue assay revealed that CX43 deletion enhanced the depressor effect of miR-139-5p on ECV-304 cell proliferation (P < 0.01), invasion (P = 0.028), and migration (P = 0.014).Conclusion:MiR-139-5p, as a tumor-suppressor, repressed cell proliferation, i...

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Epac1 is involved in cell cycle progression in lung cancer through PKC and Cx43 regulation

Abstract: Normal Epac1 expression may suppress lung cancer occurrence and metastasis, and its downregulation is involved in cell cycle progression in lung cancer through PKC and Cx43 regulation.

Cited by 2 publications

References 28 publications

Analysis of genomic and transcriptomic variations as prognostic signature for lung adenocarcinoma

Analysis of genomic and transcriptomic variations as prognostic signature for lung adenocarcinoma

Tumor-suppressor microRNA-139-5p restrains bladder cancer cell line ECV-304 properties via targeting Connexin 43

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