The prognostic significance of Cdc6 and Cdt1 in breast cancer

Mahadevappa, Ravikiran; Neves, Henrique; Yuen, Shun Ming; Bai, Yuchen; McCrudden, Cian M.; Yuen, Hiu Fung; Wen, Qing; Zhang, Shudong; Kwok, Hang Fai

doi:10.1038/s41598-017-00998-9

Cited by 87 publications

(76 citation statements)

References 35 publications

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“…In normal cells, cell proliferation is tightly regulated by the binding of DNA licensing factors such as CDC6, Cdt1 and Minichromosome Maintenance proteins (MCM) proteins (MCM2-7) onto DNA replication initiation sites. We, along with others, have previously observed the high expression of CDC6, CDT1 and MCM2-7 proteins in breast cancer progression [ 2 , 3 , 4 ]. Alterations in the expression profiles of the licensing proteins have been linked to various aspects of cancer [ 5 , 6 ] such as cancer cell proliferation [ 7 , 8 ] and cancer invasion [ 9 ].…”

Section: Introductionmentioning

confidence: 69%

DNA Replication Licensing Protein MCM10 Promotes Tumor Progression and Is a Novel Prognostic Biomarker and Potential Therapeutic Target in Breast Cancer

Mahadevappa

Neves

Yuen

et al. 2018

Cancers

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Breast cancer is one of the most common malignancies in women worldwide. In breast cancer, the cell proliferation rate is known to influence the cancer malignancy. Recent studies have shown that DNA replication initiation/licensing factors are involved in cancer cell proliferation as well as cancer cell migration and invasion. Licensing factors have also been reported as important prognostic markers in lung, prostrate, and bladder cancers. Here, we studied the role of MCM10, a novel licensing factor, in breast cancer progression. From the public database, NCBI, we investigated six independent breast cancer patient cohorts, totaling 1283 patients. We observed a significant association between high MCM10 mRNA expression with tumor grading and patients’ survival time. Most importantly, using breast cancer cohorts with available treatment information, we also demonstrated that a high level of MCM10 is associated with a better response to conventional treatment. Similarly, in in vitro studies, the expression level of MCM10 in breast cancer cell lines is significantly higher compared to paired normal breast epithelium cells. Knockdown of MCM10 expression in the cancer cell line showed significantly decreased tumorigenic properties such as cell proliferation, migration and anchorage independence. The MCF7 breast cancer cell line, after MCM10 expression knockdown, showed significantly decreased tumorigenic properties such as cell proliferation, migration, and anchorage independent growth. Mechanistically, MCM10 expression is observed to be regulated by an Estrogen Receptor (ER) signaling pathway, where its expression is suppressed by the inhibition of the ER or serum withdrawal. Our results suggest that MCM10 plays an important role in breast cancer progression and is a potential prognostic/predictive biomarker and therapeutic target for breast cancer patients.

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Section: Introductionmentioning

confidence: 69%

DNA Replication Licensing Protein MCM10 Promotes Tumor Progression and Is a Novel Prognostic Biomarker and Potential Therapeutic Target in Breast Cancer

Mahadevappa

Neves

Yuen

et al. 2018

Cancers

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“…The subcellular translocation of this protein during cell cycle is regulated through phosphorylation by Cdks. 25 CDC6 dysregulated is associated with many types of human malignancies including breast cancer, 26 prostate cancer, 27 ovarian cancer 28 as well as lung cancer 29 and osteosarcoma. 30 In addition, CDC6 may be a promising target for overcoming CDDP resistance in bladder cancer, 31 oxaliplatin resistance for CRC 32 and paclitaxel resistance for gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

<p>Potential Prognostic and Diagnostic Values of CDC6, CDC45, ORC6 and SNHG7 in Colorectal Cancer</p>

Hu¹,

Wang²,

Li³

et al. 2019

OTT

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Background: Colorectal cancer (CRC) is a common human malignancy. The aims of this study are to investigate the gene expression profile of CRC and to explore potential strategy for CRC diagnosis, therapy and prognosis. Methods: We use affy and Limma package of Bioconductor R to do differential expression genes (DEGs) and differential expression lncRNAs (DELs) analysis from the gene datasets (GSE8671, GSE21510, GSE32323, GSE39582 and TCGA) respectively. Then, DEGs were analyzed by GO and KEGG pathway and Kaplan-Meier survival curve and Cox regression analyses were used to find aberrantly expressed genes associated with survival outcome of CRC patients. Real-time PCR assay was used to verify the aberrantly expressed genes expression in CRC samples. Results: 306 up-regulation and 213 down-regulation common DEGs were found. A total of 485 DELs were identified, of which 241 up-regulated and 244 down-regulated. Then, GO and KEGG pathway analyses showed that DEGs were involved in cell cycle, mineral absorption, DNA replication, and Nitrogen metabolism. Among them, Kaplan-Meier survival curve and Cox regression analyses revealed that CDC6, CDC45, ORC6 and SNHG7 levels were significantly associated with survival outcome of CRC patients. Finally, real-time PCR assay was used to verify that the CDC6, CDC45, ORC6 and SNHG7 expression were upregulated in 198 CRC samples compared with the expression levels in individual-matched adjacent mucosa samples. Conclusion: CDC6, CDC45, ORC6 and SNHG7 are implicated in CRC initiation and progression and could be explored as potential diagnosis, therapy and prognosis targets for CRC.

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“…Particularly, three formerly validated direct targets of hsa-miR-886-3p, PLK1, TGFB1 and CDC6 [25,28], are downregulated upon snc886-3p overexpression. Additionally, candidate snc886-3p direct target CDT1, which is a partner of CDC6, has been associated with cell cycle impairment [55]. A more detailed picture of the snc886-3p responsive genes belonging to the KEGG cell cycle pathway highlights additional downregulated genes ( Figure S2D).…”

Section: Snc886-3p Modulates Transcripts Affecting Cell Cycle and Apomentioning

confidence: 99%

vtRNA2-1/nc886 Produces a Small RNA That Contributes to Its Tumor Suppression Action through the microRNA Pathway in Prostate Cancer

Fort

Garat

Sotelo‐Silveira

et al. 2020

ncRNA

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vtRNA2-1 is a vault RNA initially classified as microRNA precursor hsa-mir-886 and recently proposed as “nc886”, a new type of non-coding RNA involved in cancer progression acting as an oncogene and tumor suppressor gene in different tissues. We have shown that vtRNA2-1/nc886 is epigenetically repressed in neoplastic cells, increasing cell proliferation and invasion in prostate tissue. Here we investigate the ability of vtRNA2-1/nc886 to produce small-RNAs and their biological effect in prostate cells. The interrogation of public small-RNA transcriptomes of prostate and other tissues uncovered two small RNAs, snc886-3p and snc886-5p, derived from vtRNA2-1/nc886 (previously hsa-miR-886-3p and hsa-miR-886-5p). Re-analysis of PAR-CLIP and knockout of microRNA biogenesis enzymes data showed that these small RNAs are products of DICER, independent of DROSHA, and associate with Argonaute proteins, satisfying microRNA attributes. In addition, the overexpression of snc886-3p provokes the downregulation of mRNAs bearing sequences complementary to its “seed” in their 3′-UTRs. Microarray and in vitro functional assays in DU145, LNCaP and PC3 cell lines revealed that snc886-3p reduced cell cycle progression and increases apoptosis, like its precursor vtRNA2-1/nc886. Finally, we found a list of direct candidate targets genes of snc886-3p upregulated and associated with disease condition and progression in PRAD-TCGA data. Overall, our findings suggest that vtRNA2-1/nc886 and its processed product snc886-3p are synthesized in prostate cells, exerting a tumor suppressor action.

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The prognostic significance of Cdc6 and Cdt1 in breast cancer

Cited by 87 publications

References 35 publications

DNA Replication Licensing Protein MCM10 Promotes Tumor Progression and Is a Novel Prognostic Biomarker and Potential Therapeutic Target in Breast Cancer

DNA Replication Licensing Protein MCM10 Promotes Tumor Progression and Is a Novel Prognostic Biomarker and Potential Therapeutic Target in Breast Cancer

<p>Potential Prognostic and Diagnostic Values of CDC6, CDC45, ORC6 and SNHG7 in Colorectal Cancer</p>

vtRNA2-1/nc886 Produces a Small RNA That Contributes to Its Tumor Suppression Action through the microRNA Pathway in Prostate Cancer

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