The RNA-Binding Protein HuR Confers Oxaliplatin Resistance of Colorectal Cancer By Upregulating CDC6

Cai, Jian; Wang, Huaiming; Jiao, Xiao‐Dong; Huang, Rongkang; Qin, Qiyuan; Zhang, Jianwei; Chen, Honglei; Feng, Dan; Tian, Xin

doi:10.1158/1535-7163.mct-18-0945

Cited by 37 publications

(30 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cdc6 depletion not only inhibited cell proliferation but also resulted in G 2 /M cell cycle arrest with upregulation of p-histone H3 and cyclin A2 in PC cells. Similar to our results, Cdc6 downregulation inhibited cell proliferation, DNA synthesis, epithelial-mesenchymal transition (EMT), migration, and invasion in human colorectal cancer 30 . Also, Cdc6 was reported to be highly expressed in osteosarcoma patients and osteosarcoma cell lines, and proliferation was inhibited in MG63 cells due to the deficiency of Cdc6 29 .…”

Section: Discussionsupporting

confidence: 91%

Cdc6 disruption leads to centrosome abnormalities and chromosome instability in pancreatic cancer cells

Youn

Lee

Kim

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Cell division cycle 6 (Cdc6) plays key roles in regulating DNA replication, and activation and maintenance of cell cycle check points. In addition, Cdc6 exerts oncogenic properties via genomic instability associated with incomplete DNA replication. This study aimed to examine the effects of Cdc6 on pancreatic cancer (PC) cells. Our results showed that Cdc6 expression was higher in clinical PC specimens (based on analysis of the GEPIA database) and cell lines, and the high Cdc6 expression was associated with poorer survival in The Cancer Genome Atlas-PC cohort. In addition, Cdc6-depleted PC cells significantly inhibited cell proliferation and colony formation, delayed G2/M cell cycle progression, and increased expression of p-histone H3 and cyclin A2 levels. These observations could be explained by Cdc6 depletion leading to multipolar and split spindles via centrosome amplification and microtubule disorganization which eventually increases chromosome missegregation. Furthermore, Cdc6-depleted PC cells showed significantly increased apoptosis, which was consistent with increased caspase-9 and caspase-3 activation. Collectively, our results demonstrated that Cdc6-depleted PC cells are arrested in mitosis and eventually undergo cell death by induced multipolar spindles, centrosome aberrations, microtubule disorganization, and chromosome instability. In conclusion, Cdc6 may be a potential biomarker and therapeutic target for PC.

show abstract

Section: Discussionsupporting

confidence: 91%

Cdc6 disruption leads to centrosome abnormalities and chromosome instability in pancreatic cancer cells

Youn

Lee

Kim

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…As reported before, HuR could regulate CDC6 via binding to its 3ʹUTR regions. 20 HuR was identified as a member of the embryonic lethal abnormal vision (ELAV) family of RNA-binding proteins (RBPs) and was able to selectively bind to AU-rich elements (ARE) in the 3ʹ untranslated regions (3ʹ-UTR) of target mRNAs to antagonize AREmediated mRNA degradation, leading to prolonged mRNA half-lives and increased translation. 21,22 Genes upregulated by HuR include cancer-trait proteins that promote cell proliferation and survival, local angiogenesis, as well as those that facilitate cancer cell invasion, metastasis, and evasion of immune recognition.…”

Section: Discussionmentioning

confidence: 99%

<p>Long-Noncoding RNA CASC9 Promotes Progression of Non-Small Cell Lung Cancer by Promoting the Expression of CDC6 Through Binding to HuR</p>

Zhang

Lian²,

Fan³

et al. 2020

CMAR

View full text Add to dashboard Cite

The long-noncoding RNAs (lncRNAs) have been identified as key players in diverse cellular processes in non-small cell lung cancer (NSCLC). However, the understanding of biological functions and detailed mechanisms of lncRNAs is still limited. Herein, the lncRNA cancer susceptibility candidate 9 (CASC9) on NSCLC progression is investigated. Materials and Methods: Expressions of CASC9, HuR and cell division cycle 6 (CDC6) in NSCLC tissues were detected with quantitative real-time polymerase chain reaction (qRT-PCR). The cell counting kit-8, transwell assays, and flow cytometry were used to examine cell proliferation, migration, and the cell cycle. Tumor growth in vivo was evaluated by xenograft tumor experiments and immunohistochemistry. RNA-binding protein immunoprecipitation (RIP) was used to identify the interaction between HuR and CDC6, and CASC9 and HuR. Results: CASC9, CDC6 and HuR expression were found significantly upregulated in NSCLC tissues, which predicted poorer 5-year overall survival in NSCLC patients. Inhibition of CASC9 significantly reduced the malignancy of NSCLC cells, such as proliferation, migration and cell cycle. In vivo experiments further demonstrated that CASC9 knockdown reduced the tumor growth and the Ki-67 expression. Moreover, CASC9 knockdown inhibited the expression of CDC6 which was detected overexpressed in NSCLC tumor tissues. Then, up-regulation of CDC6 could partly reverse the negative effects of CASC9 on cell proliferation, migration and cell cycle. RIP assay and rescue experiment showed that CASC9 regulated CDC via binding to HuR. Conclusion: Our results indicate that CASC9 conferred an aggressive phenotype in NSCLC and might be a pivotal target for this disease.

show abstract

“…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. 33 As a DNA replication initiation factor, Cdc45 directly interacts with MCM7 and DNA polymerase alpha in the assembly of the highly conserved multiprotein complex that includes Cdc6/Cdc18, the MCMs, and DNA polymerase; the assembly of the complex is essential for the initiation of eukaryotic DNA replication.…”

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

View full text Add to dashboard Cite

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.

show abstract

The RNA-Binding Protein HuR Confers Oxaliplatin Resistance of Colorectal Cancer By Upregulating CDC6

Cited by 37 publications

References 47 publications

Cdc6 disruption leads to centrosome abnormalities and chromosome instability in pancreatic cancer cells

Cdc6 disruption leads to centrosome abnormalities and chromosome instability in pancreatic cancer cells

<p>Long-Noncoding RNA CASC9 Promotes Progression of Non-Small Cell Lung Cancer by Promoting the Expression of CDC6 Through Binding to HuR</p>

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

Contact Info

Product

Resources

About