NCALD affects drug resistance and prognosis by acting as a ceRNA of CX3CL1 in ovarian cancer

Dong, Caihua; Yin, Fuqiang; Zhu, Dong; Cai, Xiangxue; Chen, Cuilan; Liu, Xia

doi:10.1002/jcb.29670

Cited by 16 publications

(19 citation statements)

References 49 publications

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“…Overexpressing miR-181d inhibits metastasis of CRC cells through PEAK1 (57). In addition, previous studies have shown that NCALD may regulate chemo-resistance by the ERK1/2, NF-κB and immune response pathways (58) and prognosis via CX3CL1 in ovarian cancer (59). The results of the present study demonstrated that exosomal miR-181d-5p binds directly with NCALD to regulate 5-FU sensitivity.…”

Section: Discussionsupporting

confidence: 68%

N6‑methyladenosine upregulates miR‑181d‑5p in exosomes derived from cancer‑associated fibroblasts to inhibit 5‑FU sensitivity by targeting NCALD in colorectal cancer

Pan

Deng

et al. 2022

Int J Oncol

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Resistance to 5-Fluorouracil (5-FU) is a frequent occurrence in patients with colorectal cancer (CRC). MicroRNAs (miRNAs) from cancer-associated fibroblasts (CAFs)-secreted exosomes have been associated with 5-FU sensitivity. The potential molecular mechanism of CAFs-exosomal miRNAs in CRC remains unclear. The aim of the present study was to elucidate the role of exosomal miRNAs in 5-FU sensitivity in CRC. Exosomes derived from CAFs were extracted. Exosomal miR-181d-5p was identified as a miRNA associated with 5-FU sensitivity. The putative function of exosomal miR-181d-5p was evaluated by ethynyl-2-deoxyuridine staining, flow cytometry, RNA immunoprecipitation, luciferase reporter assay, tumor xenograft formation, reverse transcription-quantitative PCR and western blot analysis. Modification of miR-181d-5p by the RNA N6-methyladenosine (m 6 A) methyltransferase like (METTL)3 was examined by m 6 A methylation analysis. The results indicated that m 6 A modification and METTL3 expression were upregulated in CRC patients. METTL3-dependent m 6 A methylation promoted the miR-181b-5p process by DiGeorge Syndrome Critical Region 8 (DGCR8) in CAFs. CAFs-derived exosomes inhibited 5-FU sensitivity in CRC cells through the METTL3/miR-181d-5p axis. A mechanistic study revealed that miR-181d-5p directly targeted neurocalcin δ (NCALD) to inhibit the 5-FU sensitivity of CRC cells. Patients with higher NCALD levels exhibited a higher survival rate. Taken together, METTL3-dependent m 6 A methylation was upregulated in CRC to promote the processing of miR-181d-5p by DGCR8. This led to increased miR-181d-5p expression, which inhibited the 5-FU sensitivity of CRC cells by targeting NCALD. The results of the present study provided novel insight into exosomal microRNAs in 5-FU sensitivity in CRC cells. Furthermore, exosomal miR-181d-5p may represent a potential prognostic marker for CRC.

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Section: Discussionsupporting

confidence: 68%

N6‑methyladenosine upregulates miR‑181d‑5p in exosomes derived from cancer‑associated fibroblasts to inhibit 5‑FU sensitivity by targeting NCALD in colorectal cancer

Pan

Deng

et al. 2022

Int J Oncol

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“…TCGA data found that the expression of NCALD in platinum-resistant patients was lower than that in platinum-sensitive patients. Patients with low NCALD expression have poor overall survival (OS) and progression-free survival (PFS) [ 74 ]. Our findings are consistent with this report.…”

Section: Discussionmentioning

confidence: 99%

Abnormal methylation characteristics predict chemoresistance and poor prognosis in advanced high-grade serous ovarian cancer

et al. 2021

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Background Primary or acquired chemoresistance is a key link in the high mortality rate of ovarian cancer. There is no reliable method to predict chemoresistance in ovarian cancer. We hypothesized that specific methylation characteristics could distinguish chemoresistant and chemosensitive ovarian cancer patients. Methods In this study, we used 450 K Infinium Methylation BeadChip to detect the different methylation CpGs between ovarian cancer patients. The differential methylation genes were analyzed by GO and KEGG Pathway bioinformatics analysis. The candidate CpGs were confirmed by pyrosequencing. The expression of abnormal methylation gene was identified by QRT-PCR and IHC. ROC analysis confirmed the ability to predict chemotherapy outcomes. Prognosis was evaluated using Kaplan–Meier. Results In advanced high-grade serous ovarian cancer, 8 CpGs (ITGB6:cg21105318, cg07896068, cg18437633; NCALD: cg27637873, cg26782361, cg16265707; LAMA3: cg20937934, cg13270625) remained hypermethylated in chemoresistant patients. The sensitivity, specificity and AUC of 8 CpGs (ITGB6:cg21105318, cg07896068, cg18437633; NCALD: cg27637873, cg26782361, cg16265707; LAMA3: cg20937934, cg13270625) methylation to predict chemotherapy sensitivity were 63.60–97.00%, 46.40–89.30% and 0.774–0.846. PFS of 6 candidate genes (ITGB6:cg21105318, cg07896068; NCALD: cg27637873, cg26782361, cg16265707; LAMA3: cg20937934) hypermethylation patients was significantly shorter. The expression of NCALD and LAMA3 in chemoresistant patients was lower than that of chemosensitive patients. Spearman analysis showed that NCALD and LAMA3 methylations were negatively correlated with their expression. Conclusions As a new biomarker of chemotherapy sensitivity, hypermethylation of NCALD and LAMA3 is associated with poor PFS in advanced high-grade serous ovarian cancer. In the future, further research on NCALD and LAMA3 will be needed to provide guidance for clinical stratification of demethylation therapy.

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“…An increasing number of studies have indicated that ceRNA-related genes strongly impact cancer pathogenesis, progression and prognosis (28). Regarding OC, several studies have explored ceRNA networks in OC based on TCGA (17) and Gene Expression Omnibus (29) data and these studies predominantly focused on certain clinical traits in the OC cohort, such as recurrence (30) and drug resistance (31). However, this is far from ideal, as differential expression between OC and healthy tissues was not considered.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of competitive endogenous RNAs networks reveals potential prognostic biomarkers associated with epithelial ovarian cancer

Gao

Chen

et al. 2021

Oncol Lett

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Ovarian cancer (OC) is a major health threat to females, as it has high morbidity and mortality. Evidence has increasingly demonstrated that long non-coding RNAs (lncRNAs) regulate OC progression and they may have value as early diagnostic biomarkers, prognostic biomarkers and/or therapeutic targets. In the present study, the regulatory mechanisms and prognosis associated with cancer-specific lncRNAs and their related competing endogenous (ce)RNA network in OC were investigated. The differential expression profiles and prognostic significance of lncRNAs and mRNAs were systematically explored based on data from 359 OC cases from The Cancer Genome Atlas and 180 healthy individuals from the Genotype-Tissue Expression database. Functional enrichment analyses, RNA-RNA interactome prediction, ceRNA network analysis, correlation analysis and survival analysis were utilized to identify hub lncRNAs and biomarkers associated with OC diagnosis or prognosis. A total of 1,049 differentially expressed lncRNAs and 6,516 differentially expressed mRNAs between OC and healthy tissues were detected. An lncRNA-micro (mi)RNA-mRNA regulatory network in OC was further established, containing 91 lncRNAs, 23 miRNAs and 179 mRNAs. After survival analysis based on the expression of the RNAs in the ceRNA network, 8 lncRNAs, 4 miRNAs and 11 mRNAs that were significantly associated with OC patient survival (P<0.05) were obtained. Using least absolute shrinkage and selection operator-penalized Cox regression, an eight-lncRNA risk score model was generated, which was able to readily discriminate between OC and healthy individuals and predict the survival of patients with OC. In addition, the differential expression of several key lncRNAs and mRNAs was verified by reverse transcription-quantitative PCR and western blot analysis. The current study presents a novel lncRNA-miRNA-mRNA network, which provides insight into the potential pathogenesis of OC and allows the identification of prognostic biomarkers and treatment strategies for OC.

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NCALD affects drug resistance and prognosis by acting as a ceRNA of CX3CL1 in ovarian cancer

Cited by 16 publications

References 49 publications

N6‑methyladenosine upregulates miR‑181d‑5p in exosomes derived from cancer‑associated fibroblasts to inhibit 5‑FU sensitivity by targeting NCALD in colorectal cancer

N6‑methyladenosine upregulates miR‑181d‑5p in exosomes derived from cancer‑associated fibroblasts to inhibit 5‑FU sensitivity by targeting NCALD in colorectal cancer

Abnormal methylation characteristics predict chemoresistance and poor prognosis in advanced high-grade serous ovarian cancer

Comprehensive analysis of competitive endogenous RNAs networks reveals potential prognostic biomarkers associated with epithelial ovarian cancer

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