Relapse-associated microRNA in gastric cancer patients after S-1 adjuvant chemotherapy

Omura, Tetsuya; Shimada, Yutaka; Nagata, Takuya; Okumura, Tomoyuki; Fukuoka, Junya; Yamagishi, Fuminori; Tajika, Sadakatsu; Nakajima, Saeko; Kawabe, Akira; Tsukada, Kazuhiro

doi:10.3892/or.2013.2900

Cited by 23 publications

(26 citation statements)

References 24 publications

(23 reference statements)

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“…Its downregulation in tumoral versus normal tissue has been reported in osteosarcoma [21], in colorectal cancer [13, 22], hepatocarcinoma [14] and gastric tumors [23]. A low expression of miR-422a is a marker of poor prognosis in osteosarcoma [21] and colorectal cancer [24] and of poor RFS in hepatocarcinoma [25].…”

Section: Discussionmentioning

confidence: 99%

MiR-422a promotes loco-regional recurrence by targeting NT5E/CD73 in head and neck squamous cell carcinoma

et al. 2016

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At the time of diagnosis, 60% of patients with head and neck squamous cell carcinoma (HNSCC) present tumors in an advanced stage (III-IV) of disease and 80% will relapse within the first two years post-treatment, due to their frequent radio(chemo)resistance. To identify new molecular targets and companion biomarkers, we have investigated the miRNome of 75 stage III-IV oropharynx tumors without relapse (R) or with loco-regional relapse (non-responder, NR) within two years post-treatment. Interestingly, miR-422a was significantly downregulated in NR tumors, in agreement with the increase in cell proliferation and adhesion induced by miR-422a inhibition in vitro. Furthermore, we identified CD73/NT5E oncogene as target of miR-422a. Indeed, modulation of the endogenous level of miR-422a inversely influences the expression and the enzymatic activity of CD73. Moreover, knocking down CD73 mimics the effects of miR-422a upregulation. Importantly, in tumors, miR-422a and CD73 expression levels are inversely correlated, and both are predictive of relapse free survival - especially considering loco(regional) recurrence - in vitro two independent cohorts of advanced oropharynx or HNSCC (N=255) tumors. In all, we reported, for the first time, that MiR-422a and its target CD73 are involved in early loco(regional) recurrence of HNSCC tumors and are new targets for personalized medicine.

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Section: Discussionmentioning

confidence: 99%

MiR-422a promotes loco-regional recurrence by targeting NT5E/CD73 in head and neck squamous cell carcinoma

et al. 2016

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“…A few studies have revealed the involvement of miR-422a in human cancers. It is dysregulated in osteosarcoma [19], colorectal cancer [20–22], hepatocarcinoma [23], and gastric cancer [24]. miR-422a is an indicative marker for poor prognosis in osteosarcoma, gastric cancer, and hepatocarcinoma [23].…”

Section: Discussionmentioning

confidence: 99%

Circulating microRNA-422a is associated with lymphatic metastasis in lung cancer

Zhao

et al. 2017

Oncotarget

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To identify specific circulating microRNAs that were associated with the lymphatic metastasis in lung cancer, we performed miRNA microarray analysis of lymph node with and without metastasis from five lung cancer patients. Top six differentially expressed miRNAs were selected for further validation. A training cohort of 26 patients with lung cancer was firstly recruited and the selected miRNAs in the plasma samples were investigated. miRNA-422a, with highest diagnostic accuracy in lymphatic metastasis was identified (AUC, area under the receiver operating characteristic curve, 0.744; 95%CI, 0.570-0.918). The diagnostic value of miR-422a was also demonstrated by a validation cohort of 51 lung cancer patients (AUC, 0.880; 95%CI, 0.787-0.972). Moreover, a high diagnostic value was also observed after integrated analysis of training and validation cohorts (AUC, 0.792; 95%CI, 0.688-0.896). The odds ratio of high miR-422a expression for lymphatic metastasis in lung cancer was 13.645 (95%CI, 2.677-69.553) after adjustment of the potential confounding factors. Furthermore, we predicted the target genes of miR-422a by combining the online database, miRcords, and the data from GEO and TCGA. Sixty-one target genes of miR-422a that might be involved in lymphatic metastasis in lung cancer were identified. And GO analysis suggested multiple target genes relatively concentrated in the biological processes of apoptosis, transport, and protein phosphorylation.

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“…Pouladi et al (59) predicted a binding site for miR-4732-5p in the 5′ UTR of telomerase cajal body protein 1 mRNA. In addition, miR-4732-5p has been revealed to be closely associated with recurrence in gastric cancer patients treated with S-1 adjuvant chemotherapy (60). Importantly, the TF-mRNA regulatory network constructed in the present study revealed that the target genes of the miRNAs investigated were potentially regulated by numerous transcription factors, which highlights the critical roles of these miRNAs and their targets in physiological and pathological processes.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of dysregulated microRNAs in the nipple discharge of patients with breast cancer

Zhang

Wang

2017

Oncology Letters

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Abstract. MicroRNAs (miRNAs/miRs) have been reported to be associated with the tumorigenesis and progression of various types of human cancer; however, the underlying mechanisms of this association remain unclear. The aim of the present study was to explore the potential functions of miRNAs in the development of breast cancer using bioinformatics analysis, based on the miRNA expression profile in nipple discharge. A previous study demonstrated the upregulation of miR-3646 and miR-4484, and the downregulation of miR-4732-5p in the nipple discharge of patients with breast cancer, compared with patients with benign breast lesions. In the present study, the target genes of miR-3646, -4484 and -4732-5p were predicted using TargetScan and the MicroRNA Target Prediction and Functional Study Database. The predicted target genes were further analyzed by Gene Ontology term enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and protein-protein interaction analysis. Numerous carcinoma-associated genes, including ADIPOQ, CPEB1, DNAJB4, EIF4E, APP and BCLAF1, were revealed to be putative targets of miR-3646, -4484 and -4732-5p. Bioinformatics analysis associated miR-3646 with the Rap1 and TGF-β signaling pathways, miR-4484 with the ErbB, estrogen and focal adhesion signaling pathways, and miR-4732-5p with the proteoglycan signaling pathway. Notably, protein-protein interaction analysis identified that numerous predicted targets of these miRNAs were associated with one other. In addition, the target genes of the miRNAs were identified to be under the regulation of a number of transcription factors (TFs). The predicted target genes of miR-3646, -4484 and -4732-5p were identified to serve a role in cancer-associated signaling pathways and TF-mRNA networks, indicating that they serve a role in breast carcinogenesis and progression. These results provide a comprehensive view of the functions and molecular mechanisms of miR-3646, -4484 and -4732-5p, and will aid in future studies.

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Relapse-associated microRNA in gastric cancer patients after S-1 adjuvant chemotherapy

Cited by 23 publications

References 24 publications

MiR-422a promotes loco-regional recurrence by targeting NT5E/CD73 in head and neck squamous cell carcinoma

MiR-422a promotes loco-regional recurrence by targeting NT5E/CD73 in head and neck squamous cell carcinoma

Circulating microRNA-422a is associated with lymphatic metastasis in lung cancer

Bioinformatics analysis of dysregulated microRNAs in the nipple discharge of patients with breast cancer

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