Cyclin G2: A novel independent prognostic marker in pancreatic cancer

Hasegawa, Shinobu; Nagano, Hiroaki; Konno, Masamitsu; Eguchi, Hidetoshi; Tomokuni, Akira; Tomimaru, Yoshito; Wada, Hiroshi; Hama, Naoki; Kikuchi, Kôichi; Kobayashi, Shogo; Marubashi, Shigeru; Nishida, Naohiro; Koseki, Junichi; Gotoh, Noriko; Ohno, Shouichi; Yabuta, Norikazu; Nishimura, Hiroshi; Mori, Masaki; Doki, Yuichiro; Ishii, Hideshi

doi:10.3892/ol.2015.3667

Cited by 21 publications

(15 citation statements)

References 23 publications

(41 reference statements)

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“…While ALDH1A1 and MYC genes were reported in metastasis of several tumor types and associated with poor prognosis [ 39 , 45 , 47 , 62 , 63 ], for CCNG2, a cell cycle checkpoint cyclin upregulated in response to DNA damage, the association to stemness was not clear. It was reported to have tumor suppressor functions in different neoplasias [ 64 , 65 ], although, supporting our observations, CCNG2 positively associated with prostate cancer recurrence after radical prostatectomy [ 46 ]. CCNG2 induces microtubule bundling and stability, and contributes to resistance to chemotherapy, presumably by facilitating a delay in the transition from G1/S to G2/M phase that allow reorganization of microtubules and chromatin repairs after drug exposure [ 34 , 66 – 68 ].…”

Section: Discussionsupporting

confidence: 84%

Prostate Tumor Overexpressed-1 (PTOV1) promotes docetaxel-resistance and survival of castration resistant prostate cancer cells

et al. 2017

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Metastatic prostate cancer is presently incurable. The oncogenic protein PTOV1, first described in prostate cancer, was reported as overexpressed and significantly correlated with poor survival in numerous tumors. Here, we investigated the role of PTOV1 in prostate cancer survival to docetaxel and self-renewal ability. Transduction of PTOV1 in docetaxel-sensitive Du145 and PC3 cells significantly increased cell survival after docetaxel exposure and induced docetaxel-resistance genes expression (ABCB1, CCNG2 and TUBB2B). In addition, PTOV1 induced prostatospheres formation and self-renewal genes expression (ALDH1A1, LIN28A, MYC and NANOG). In contrast, Du145 and PC3 cells knockdown for PTOV1 significantly accumulated in the G2/M phase, presented a concomitant increased subG1 peak, and cell death by apoptosis. These effects were enhanced in docetaxel-resistant cells. Analyses of tumor datasets show that PTOV1 expression significantly correlated with prostate tumor grade, drug resistance (CCNG2) and self-renewal (ALDH1A1, MYC) markers. These genes are concurrently overexpressed in most metastatic lesions. Metastases also show PTOV1 genomic amplification in significant co-occurrence with docetaxel-resistance and self-renewal genes. Our findings identify PTOV1 as a promoter of docetaxel-resistance and self-renewal characteristics for castration resistant prostate cancer. The concomitant increased expression of PTOV1, ALDH1A1 and CCNG2 in primary tumors, may predict metastasis and bad prognosis.

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Section: Discussionsupporting

confidence: 84%

Prostate Tumor Overexpressed-1 (PTOV1) promotes docetaxel-resistance and survival of castration resistant prostate cancer cells

et al. 2017

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“…The current literature suggests that CCNG2 plays an important inhibitory role in cancer initiation and progression [60]. It has been shown that CCNG2 dysregulation is related to cancer progression and could play an important role in cell transformation and the early stages of cancer development [60,61]. Seemingly, our findings would seem to contrast with the role played by CCNG2 in cancer.…”

Section: Discussioncontrasting

confidence: 72%

Identification of Novel Markers of Prostate Cancer Progression, Potentially Modulated by Vitamin D

et al. 2019

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Prostate cancer (PCa) is one of the most common cancers in men. The main risk factors associated with the disease include older age, family history of the disease, smoking, alcohol and race. Vitamin D is a pleiotropic hormone whose low levels are associated with several diseases and a risk of cancer. Here, we undertook microarray analysis in order to identify the genes involved in PCa. We analyzed three PCa microarray datasets, overlapped all genes significantly up-regulated, and subsequently intersected the common genes identified with the down-regulated genes transcriptome of LNCaP cells treated with 1α,25(OH)2D3, in order to identify the common genes involved in PCa and potentially modulated by Vitamin D. The analysis yielded 43 genes potentially involved in PCa and significantly modulated by Vitamin D. Noteworthy, our analysis showed that six genes (PRSS8, SOX4, SMYD2, MCCC2, CCNG2 and CD2AP) were significantly modulated. A Pearson correlation analysis showed that five genes out of six (SOX4 was independent), were statistically correlated with the gene expression levels of KLK3, and with the tumor percentage. From the outcome of our investigation, it is possible to conclude that the genes identified by our analysis are associated with the PCa and are potentially modulated by the Vitamin D.

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“…Unlike other cyclins, the expression of cyclin G2 increases in cycle‐arrested and terminally differentiated cells . A large body of evidence indicates that cyclin G2 acts as an important tumour suppressor . Recent findings have suggested that the expression of cyclin G2 in fatty tissues of obese patients is associated with steady‐state of carbohydrate metabolism in the body .…”

Section: Introductionmentioning

confidence: 99%

“…1,2 A large body of evidence indicates that cyclin G2 acts as an important tumour suppressor. [3][4][5][6] Recent findings have suggested that the expression of cyclin G2 in fatty tissues of obese patients is associated with steady-state of carbohydrate metabolism in the body. 7 Furthermore, in patients with type 2 diabetes, the level of cyclin G2 is positively correlated with that of insulin-degrading enzyme (IDE).…”

Section: Introductionmentioning

confidence: 99%

Cyclin G2 regulates canonical Wnt signalling via interaction with Dapper1 to attenuate tubulointerstitial fibrosis in diabetic nephropathy

Zhao

Gao

et al. 2020

J Cellular Molecular Medi

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Cyclin G2 (CCNG2) is an atypical cyclin that inhibits cell cycle progression and is often dysregulated in human cancers. Cyclin G2 in the occurrence and development of diabetic nephropathy (DN), one of the most severe diabetic complications, has not been fully identified. In this study, we investigated the function and regulatory mechanism of cyclin G2 in DN. In vivo studies revealed that a deficiency of cyclin G2 significantly increased albuminuria and promoted tubulointerstitial fibrosis in established DN. Cyclin G2 regulated the expression of fibrosis‐related proteins via the canonical Wnt signalling pathway in renal tubular epithelial cells. Moreover, the binding of cyclin G2 to Dapper1 (Dpr1/DACT1), a protein involved in Wnt signalling, decreased the phosphorylation of Dpr1 at Ser762 by casein kinase 1 (CK1) and suppressed the Wnt signalling pathway. These findings reveal that cyclin G2 can protect against renal injury and fibrosis associated with DN and, thus, is a new target for the prevention and treatment of diabetic complications.

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Cyclin G2: A novel independent prognostic marker in pancreatic cancer

Cited by 21 publications

References 23 publications

Prostate Tumor Overexpressed-1 (PTOV1) promotes docetaxel-resistance and survival of castration resistant prostate cancer cells

Prostate Tumor Overexpressed-1 (PTOV1) promotes docetaxel-resistance and survival of castration resistant prostate cancer cells

Identification of Novel Markers of Prostate Cancer Progression, Potentially Modulated by Vitamin D

Cyclin G2 regulates canonical Wnt signalling via interaction with Dapper1 to attenuate tubulointerstitial fibrosis in diabetic nephropathy

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