Correlation between miR-200 Family Overexpression and Cancer Prognosis

Wen, Liang; Kai-ping, Zhang; Wei, Pengfei; Hu, Yue; Peng, Yiya; Fang, Xiang; He, Guoping; Wu, Limin; Chao, Min; Wang, Jing

doi:10.1155/2018/6071826

Cited by 9 publications

(8 citation statements)

References 49 publications

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“…Reliable biomarkers are thus needed to facilitate early diagnosis and to optimize the different therapies for individual patients [ 138 ]. To this end, several studies investigated the possible role of miR-200 as novel diagnostic tools in NSCLC (reviewed in [ 139 ]).…”

Section: Circulating Mir-200 As Biomarkersmentioning

confidence: 99%

The miR-200 Family of microRNAs: Fine Tuners of Epithelial-Mesenchymal Transition and Circulating Cancer Biomarkers

Cavallari

Ciccarese

Sharova

et al. 2021

Cancers

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The miR-200 family of microRNAs (miRNAs) includes miR-200a, miR-200b, miR-200c, miR-141 and miR-429, five evolutionarily conserved miRNAs that are encoded in two clusters of hairpin precursors located on human chromosome 1 (miR-200b, miR-200a and miR-429) and chromosome 12 (miR-200c and miR-141). The mature -3p products of the precursors are abundantly expressed in epithelial cells, where they contribute to maintaining the epithelial phenotype by repressing expression of factors that favor the process of epithelial-to-mesenchymal transition (EMT), a key hallmark of oncogenic transformation. Extensive studies of the expression and interactions of these miRNAs with cell signaling pathways indicate that they can exert both tumor suppressor- and pro-metastatic functions, and may serve as biomarkers of epithelial cancers. This review provides a summary of the role of miR-200 family members in EMT, factors that regulate their expression, and important targets for miR-200-mediated repression that are involved in EMT. The second part of the review discusses the potential utility of circulating miR-200 family members as diagnostic/prognostic biomarkers for breast, colorectal, lung, ovarian, prostate and bladder cancers.

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Section: Circulating Mir-200 As Biomarkersmentioning

confidence: 99%

The miR-200 Family of microRNAs: Fine Tuners of Epithelial-Mesenchymal Transition and Circulating Cancer Biomarkers

Cavallari

Ciccarese

Sharova

et al. 2021

Cancers

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“…Moreover, we found that bile exosomal miR-200a-3p, miR-200c-3p, and serum exosomal miR-200c-3p were not only diagnostic biomarkers but also signs representing unfavorable patients’ survival, closely associated with tumor stage and tumor differentiation. Plenty of published articles showed that higher expression of miR-200 family was related to worse survival outcomes for cancer patients ( 7 , 25 ). It was reported in a meta-analysis that miR-200 expression was negatively associated with survival prognosis in all cancers combined, especially in lung and breast cancer ( 7 ).…”

Section: Discussionmentioning

confidence: 99%

Bile-derived exosome noncoding RNAs as potential diagnostic and prognostic biomarkers for cholangiocarcinoma

et al. 2022

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BackgroundCholangiocarcinoma (CCA) is one of the most aggressive malignancies, lacking novel diagnostic and prognostic biomarkers. Exosome noncoding RNAs (ncRNA) were previously proposed as a potential source of biomarkers in several cancers. This study aimed to interpret the value of specific bile-derived ncRNA as predictors for early diagnosis and prognosis of CCA.MethodsWe recruited 100 patients who received endoscopic retrograde cholangiopancreatography at our hospital for bile duct obstruction due to CCA (n = 50) and biliary stone (n = 50). They were further divided into training set and validation set (3:2). A panel of CCA-specific ncRNAs including 5 miRNAs (PMID: 30165035) and 2 lncRNAs (PMID: 29050258) were detected in both serum and bile exosomes. The diagnostic accuracy was assessed using the area under the receiver operating characteristic curve. Logistic analysis was used to classify the potential predictors of CCA and further establish the diagnostic model. And the prognostic value of the ncRNAs was also assessed.ResultsExosomes were successfully collected from bile and serum. Exosomal miR-141-3p, miR-200a-3p, miR-200c-3p in serum and bile, as well as miR-200b-3p and ENST00000588480.1 in bile showed AUCs of >0.70 in the diagnosis of CCA. Bile exosomal miR-200c-3p displayed the best diagnostic value with the AUC of 0.87. The combination of serum CA19-9 into the model could increase the AUC to 0.906. Bile exosomal miR-200a-3p and miR-200c-3p were found to be independent predictors of CCA. Among exosomal ncRNAs in human bile and blood, 3 (serum and bile exosomal miR-200c-3p, bile exosomal miR-200a-3p) showed significant value in predicting cancer recurrence and 1 (serum exosomal miR-200c-3p) had great predictive ability of cancer death. High levels of serum exosomal miR-200c-3p showed unfavorable tumor-free survival and overall survival.ConclusionThe bile exosomal miR-200 family, particularly miR-200c-3p, was verified to be a potential biomarker for the early detection of CCA. The diagnostic ability of exosomal ncRNAs in human bile is better than that in blood. Moreover, high levels of bile exosomal miR-200a-3p, miR-200c-3p, and serum exosomal miR-200c-3p represented adverse clinical outcomes.

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“…In previous studies, the miR-200 family members are regarded as epithelial markers that inhibit the EMT process by directly targeting several EMT-associated genes including ZEB1 and ZEB2 [ 22 , 40 ], and the upregulation of miR-200 family members is related to the promotion of the mesenchymal-to-epithelial transition (MET) process [ 41 ]. In contrast, accumulative data have revealed the oncogenic functions of the miR-200 family, whose members are upregulated in several cancers and are associated with poor clinical outcomes [ 42 , 43 ], suggesting a dual role for the miR-200 family in tumorigenesis. Indeed, miR-141 has been widely considered a promising biomarker for a variety of cancers, such as non-small cell lung cancer [ 44 ], colorectal cancer [ 45 ] and prostate cancer [ 46 ], and miR-141 levels are correlated with tumor metastatic progression and poor patient prognosis [ 27 , 47 – 49 ].…”

Section: Discussionmentioning

confidence: 99%

Exosomal miR-141 promotes tumor angiogenesis via KLF12 in small cell lung cancer

Mao

Zheng

et al. 2020

J Exp Clin Cancer Res

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Background Angiogenesis, a basic requirement for tumor cell survival, is considered to be a malignant characteristic of small cell lung cancer (SCLC) and is closely related to the poor outcomes of SCLC patients. miR-141 has been found to play pro- and antiangiogenic roles in different cancers, but its role in SCLC angiogenesis has never been explored. Methods Total RNA was isolated from plasm exosomes and serum of SCLC patients to examine the expression of miR-141 by qRT-PCR. Cell proliferation, invasion, migration, tube formation assay, aortic ring assay and mouse tumor model were used to investigate the effect of exosomal miR-141 in angiogenesis in vitro and in vivo. Dual-luciferase assay was conducted to explore the target gene of miR-141. Results Circulating miR-141 was upregulated in samples from 122 SCLC patients compared with those from normal volunteers and that the increase in miR-141 was significantly associated with advanced TNM stages, implying the potential oncogenic role of miR-141 in SCLC malignancy. In vitro, miR-141 that was packaged into SCLC cell-secreted exosomes and delivered to human umbilical vein vascular endothelial cells (HUVECs) via exosomes facilitated HUVEC proliferation, invasion, migration and tube formation and promoted microvessel sprouting from mouse aortic rings. Matrigel plug assays demonstrated that SCLC cell-derived exosomal miR-141 induced neoangiogenesis in vivo. Furthermore, mouse subcutaneous tumor nodules that were developed from miR-141-overexpressing SCLC cells had a higher microvessel density (MVD) and grew faster than those developed from negative control cells. KLF12 was found to be the direct target gene of miR-141 and that the proangiogenic effect of miR-141 on HUVECs was abrogated by KLF12 overexpression. Conclusions Our results demonstrate the specific function of the exosomal miR-141/KLF12 pathway in SCLC angiogenesis for the first time and provide potential novel targets for antiangiogenic therapies for SCLC patients.

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Correlation between miR-200 Family Overexpression and Cancer Prognosis

Cited by 9 publications

References 49 publications

The miR-200 Family of microRNAs: Fine Tuners of Epithelial-Mesenchymal Transition and Circulating Cancer Biomarkers

The miR-200 Family of microRNAs: Fine Tuners of Epithelial-Mesenchymal Transition and Circulating Cancer Biomarkers

Bile-derived exosome noncoding RNAs as potential diagnostic and prognostic biomarkers for cholangiocarcinoma

Exosomal miR-141 promotes tumor angiogenesis via KLF12 in small cell lung cancer

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