MicroRNA-26a/b Regulate DNA Replication Licensing, Tumorigenesis, and Prognosis by Targeting CDC6 in Lung Cancer

Zhang, Xin; Xiao, Dakai; Wang, Ziyi; Zou, Yongxin; Huang, Liyan; Wang, Lin; Deng, Qiuhua; Hui, Pei; Zhou, Jiangfen; Liang, Chun; He, Jianxing

doi:10.1158/1541-7786.mcr-13-0641

Cited by 53 publications

(52 citation statements)

References 39 publications

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“…NCBP2 and SHMT2 were significantly reduced both as transcript and protein, while MTHFD2 was reduced as transcript but not protein, after miR160 transfection (Supplementary Figure 6). Human microRNA regulation of CDC6 has already been described as a mechanism of prevention of lung cancer formation20, while PYCR1 and MTHFD2 have been shown to be required for breast tumorigenesis in vitro 21.…”

Section: Resultsmentioning

confidence: 99%

Circulating plant miRNAs can regulate human gene expression in vitro

Pastrello

Tsay

McQuaid

et al. 2016

Sci Rep

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While Brassica oleracea vegetables have been linked to cancer prevention, the exact mechanism remains unknown. Regulation of gene expression by cross-species microRNAs has been previously reported; however, its link to cancer suppression remains unexplored. In this study we address both issues. We confirm plant microRNAs in human blood in a large nutrigenomics study cohort and in a randomized dose-controlled trial, finding a significant positive correlation between the daily amount of broccoli consumed and the amount of microRNA in the blood. We also demonstrate that Brassica microRNAs regulate expression of human genes and proteins in vitro, and that microRNAs cooperate with other Brassica-specific compounds in a possible cancer-preventive mechanism. Combined, we provide strong evidence and a possible multimodal mechanism for broccoli in cancer prevention.

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Section: Resultsmentioning

confidence: 99%

Circulating plant miRNAs can regulate human gene expression in vitro

Pastrello

Tsay

McQuaid

et al. 2016

Sci Rep

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“…Besides, bladder cancer patients with Cdc6 up-regulation have significantly shorter disease free survival time than those with lower Cdc6 expression. These results are consistently with previous researches in other type of cancers, such as oral squamous cell carcinoma [19], lung carcinomas [18, 29], cervical carcinoma [17], gallbladder carcinoma [30], prostate cancer [20]. Considering that Cdc6 is normally absent in quiescent and differentiated cells, it could be specific markers for cancer cells.…”

Section: Discussionsupporting

confidence: 91%

Cdc6 contributes to cisplatin-resistance by activation of ATR-Chk1 pathway in bladder cancer cells

Chen

Xie

et al. 2016

Oncotarget

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High activation of DNA damage response is implicated in cisplatin (CDDP) resistance which presents as a serious obstacle for bladder cancer treatment. Cdc6 plays an important role in the malignant progression of tumor. Here, we reported that Cdc6 expression is up-regulated in bladder cancer tissues and is positively correlated to high tumor grade. Cdc6 depletion can attenuate the malignant properties of bladder cancer cells, including DNA replication, migration and invasion. Furthermore, higher levels of chromatin-binding Cdc6 and ATR were detected in CDDP-resistant bladder cancer cells than in the parent bladder cancer cells. Intriguingly, down-regulation of Cdc6 can enhance sensitivity to CDDP both in bladder cancer cells and CDDP-resistant bladder cancer cells. Cdc6 depletion abrogates S phase arrest caused by CDDP, leading to aberrant mitosis by inactivating ATR-Chk1-Cdc25C pathway. Our results indicate that Cdc6 may be a promising target for overcoming CDDP resistance in bladder cancer.

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“…Many miRNAs with known function are involved in cell proliferation, apoptosis, differentiation and migration, which are commonly implicated in cancer development. 15 The increasing amounts of data have shown that miRNAs can act as oncogenes or tumor suppressors and participate in cancer development and progression. 16,17 Studies on miRNAs and tumors started with large-scale screening of microarray to detect the differentially expressed miRs between tumor tissues and normal tissues aiming at developing new strategies in tumor diagnosis and treatment in clinic.…”

Section: Discussionmentioning

confidence: 99%

miR-15b regulates cisplatin resistance and metastasis by targeting PEBP4 in human lung adenocarcinoma cells

et al. 2015

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MicroRNAs (miRNAs) have been identified as important posttranscriptional regulators involved in various biological and pathological processes of cells, but their association with tumor chemoresistance has not been fully understood. We detected miR-15b expression in two lung adenocarcinoma cell lines, A549 and A549/CDDP, and then investigated the effects of miR-15b on the metastasis and the chemosensitivity of cancer cells, using both gain- and loss-of-function studies. The correlation between miR-15b level and chemoresistance was further investigated in clinical lung adenocarcinoma specimens. miR-15b was significantly upregulated in cisplatin-resistant lung adenocarcinoma A549/CDDP cells compared with parental A549 cells. miR-15b regulates epithelial-mesenchymal transition (EMT) and cisplatin resistance in vitro and modulates response of lung adenocarcinoma cells to cisplatin in vivo. Further studies identified phosphatidylethanolamine-binding protein 4 (PEBP4) as a direct and functional target of miR-15b. Small-interfering RNA-mediated PEBP4 knockdown revealed similar effects as that of ectopic miR-15b expression, whereas overexpression of PEBP4 attenuated the function of miR-15b in lung adenocarcinoma cells. Increased miR-15b expression was also detected in tumor tissues sampled from lung adenocarcinoma patients treated with cisplatin-based chemotherapy and was proved to be correlated with low expression of PEBP4, decreased sensitivity to cisplatin and poor prognosis. Our results suggest that upregulation of miR-15b could suppress PEBP4 expression and in turn contribute to chemoresistance of lung adenocarcinoma cells to cisplatin.

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MicroRNA-26a/b Regulate DNA Replication Licensing, Tumorigenesis, and Prognosis by Targeting CDC6 in Lung Cancer

Cited by 53 publications

References 39 publications

Circulating plant miRNAs can regulate human gene expression in vitro

Circulating plant miRNAs can regulate human gene expression in vitro

Cdc6 contributes to cisplatin-resistance by activation of ATR-Chk1 pathway in bladder cancer cells

miR-15b regulates cisplatin resistance and metastasis by targeting PEBP4 in human lung adenocarcinoma cells

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