Overexpression of DNAJC12 predicts poor response to neoadjuvant concurrent chemoradiotherapy in patients with rectal cancer

He, Hao; Lee, Ying-En; Chen, Hsin-Pao; Hsing, Chung-Hsi; Chang, I‐Wei; Shiue, Yow‐Ling; Lee, Sung‐Wei; Hsu, Chao‐Tien; Lin, Li‐Ching; Wu, Tingfeng; Li, Chien‐Feng

doi:10.1016/j.yexmp.2015.03.029

Cited by 23 publications

(28 citation statements)

References 27 publications

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“…High expression of the HSP40 family member DNAJC12 has been found to correlate with colorectal tumor progression and invasion and with a poor response to neoadjuvant concurrent chemoradiotherapy [ 95 ]. It is down-regulated 41-fold in NuKO cells.…”

Section: Resultsmentioning

confidence: 99%

NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes

et al. 2016

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Regulation of gene expression is one of several roles proposed for the stress-induced nucleotide diadenosine tetraphosphate (Ap4A). We have examined this directly by a comparative RNA-Seq analysis of KBM-7 chronic myelogenous leukemia cells and KBM-7 cells in which the NUDT2 Ap4A hydrolase gene had been disrupted (NuKO cells), causing a 175-fold increase in intracellular Ap4A. 6,288 differentially expressed genes were identified with P < 0.05. Of these, 980 were up-regulated and 705 down-regulated in NuKO cells with a fold-change ≥ 2. Ingenuity® Pathway Analysis (IPA®) was used to assign these genes to known canonical pathways and functional networks. Pathways associated with interferon responses, pattern recognition receptors and inflammation scored highly in the down-regulated set of genes while functions associated with MHC class II antigens were prominent among the up-regulated genes, which otherwise showed little organization into major functional gene sets. Tryptophan catabolism was also strongly down-regulated as were numerous genes known to be involved in tumor promotion in other systems, with roles in the epithelial-mesenchymal transition, proliferation, invasion and metastasis. Conversely, some pro-apoptotic genes were up-regulated. Major upstream factors predicted by IPA® for gene down-regulation included NFκB, STAT1/2, IRF3/4 and SP1 but no major factors controlling gene up-regulation were identified. Potential mechanisms for gene regulation mediated by Ap4A and/or NUDT2 disruption include binding of Ap4A to the HINT1 co-repressor, autocrine activation of purinoceptors by Ap4A, chromatin remodeling, effects of NUDT2 loss on transcript stability, and inhibition of ATP-dependent regulatory factors such as protein kinases by Ap4A. Existing evidence favors the last of these as the most probable mechanism. Regardless, our results suggest that the NUDT2 protein could be a novel cancer chemotherapeutic target, with its inhibition potentially exerting strong anti-tumor effects via multiple pathways involving metastasis, invasion, immunosuppression and apoptosis.

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Section: Resultsmentioning

confidence: 99%

NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes

et al. 2016

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“…HSP40 assists in protein folding, unfolding, translation, translocation, and degradation [11,25,26], as well as ATPase activity of HSP70 [27]. Many of the HSP40 family members are overexpressed in numerous human cancer types, such as colorectal, gastric, and lung cancers [28][29][30][31]. Clinicopathologic analyses have shown the markedly increased expression of DnaJA1 in colorectal cancer (CRC) tissues, particularly those of which had developed metastases in lymph node and distant organs.…”

Section: Oncogenic Role Of Hsp40 In Proliferation and Metastasis Of Cmentioning

confidence: 99%

Heat Shock Proteins: Agents of Cancer Development and Therapeutic Targets in Anti-Cancer Therapy

Yun

Kim

Lim

et al. 2019

Cells

187

158

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Heat shock proteins (HSPs) constitute a large family of molecular chaperones classified by their molecular weights, and they include HSP27, HSP40, HSP60, HSP70, and HSP90. HSPs function in diverse physiological and protective processes to assist in maintaining cellular homeostasis. In particular, HSPs participate in protein folding and maturation processes under diverse stressors such as heat shock, hypoxia, and degradation. Notably, HSPs also play essential roles across cancers as they are implicated in a variety of cancer-related activities such as cell proliferation, metastasis, and anti-cancer drug resistance. In this review, we comprehensively discuss the functions of HSPs in association with cancer initiation, progression, and metastasis and anti-cancer therapy resistance. Moreover, the potential utilization of HSPs to enhance the effects of chemo-, radio-, and immunotherapy is explored. Taken together, HSPs have multiple clinical usages as biomarkers for cancer diagnosis and prognosis as well as the potential therapeutic targets for anti-cancer treatment.

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“…Possible biomarkers in blood or cancer biopsies taken prior to any therapy may help to stratify the therapy or adapt the postoperative follow-up examinations in terms of frequency and invasively. Here, miRNAs are one of several possible approaches: Different possible biomarkers were associated with therapy response: fibroblast growth factor receptor 2 ( FGFR2 ) [ 26 ], β-catenin, vascular endothelial growth factor, and apoptotic protease activating factor 1 [ 27 ], expression of DNAJC12 [ 28 ], altered DNA methylation [ 29 ], and neutrophil-lymphocyte ratio [ 30 ]. Concerning survival prognosis, most studies rely on clinical parameters [ 31 , 32 , 33 ], but also some molecular parameters were evaluated [ 34 , 35 , 36 , 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of MicroRNAs in Preoperative Treated Rectal Cancer

Azizian

Epping

et al. 2016

IJMS

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Background: Patients with locally advanced rectal cancer are treated with preoperative chemoradiotherapy followed by surgical resection. Despite similar clinical parameters (uT2-3, uN+) and standard therapy, patients’ prognoses differ widely. A possible prediction of prognosis through microRNAs as biomarkers out of treatment-naïve biopsies would allow individualized therapy options. Methods: Microarray analysis of 45 microdissected preoperative biopsies from patients with rectal cancer was performed to identify potential microRNAs to predict overall survival, disease-free survival, cancer-specific survival, distant-metastasis-free survival, tumor regression grade, or nodal stage. Quantitative real-time polymerase chain reaction (qPCR) was performed on an independent set of 147 rectal cancer patients to validate relevant miRNAs. Results: In the microarray screen, 14 microRNAs were significantly correlated to overall survival. Five microRNAs were included from previous work. Finally, 19 miRNAs were evaluated by qPCR. miR-515-5p, miR-573, miR-579 and miR-802 demonstrated significant correlation with overall survival and cancer-specific survival (p < 0.05). miR-573 was also significantly correlated with the tumor regression grade after preoperative chemoradiotherapy. miR-133b showed a significant correlation with distant-metastasis-free survival. miR-146b expression levels showed a significant correlation with nodal stage. Conclusion: Specific microRNAs can be used as biomarkers to predict prognosis of patients with rectal cancer and possibly stratify patients’ therapy if validated in a prospective study.

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Overexpression of DNAJC12 predicts poor response to neoadjuvant concurrent chemoradiotherapy in patients with rectal cancer

Cited by 23 publications

References 27 publications

NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes

NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes

Heat Shock Proteins: Agents of Cancer Development and Therapeutic Targets in Anti-Cancer Therapy

Prognostic Value of MicroRNAs in Preoperative Treated Rectal Cancer

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