Decreased Expression of miR216a Contributes to Non–Small-Cell Lung Cancer Progression

Wang, Ren-Tao; Xu, Meng; Xu, Cheng-Xiong; Song, Zhigang; Jin, Hua

doi:10.1158/1078-0432.ccr-14-0517

Cited by 52 publications

(56 citation statements)

References 38 publications

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“…The identification of the upstream regulators of metastasis appears to be essential for a better understanding of cancer metastasis and subsequent therapeutic targeting. Recent studies have highlighted the roles of miRNAs in a broad range of developmental processes associated with tumorigenesis and metastasis [23, 24]. miRNAs have been found to be able to suppress multiple target genes and thereby modulate multiple steps of metastatic progression in various cancer types [25, 26] In the context of CRC, some miRNAs have been discovered to regulate different cellular behaviors that control invasion and metastasis, and their roles remain controversial.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-375 suppresses human colorectal cancer metastasis by targeting Frizzled 8

Wen

Liu

et al. 2016

Oncotarget

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microRNAs are aberrantly expressed during the development and progression of a variety of human cancers, including colorectal cancer (CRC). Of these microRNAs, microRNA-375 (miR-375) was previously observed to be downregulated in human colorectal cancer(CRC) plasma and tissues, but its functions are largely unknown. Here, we investigated the impact of miR-375 on CRC metastasis. Specifically, miR-375 expression was significantly decreased in human CRC tissues compared with their matched noncancerous tissues (NCTs), and low levels of miR-375 predicted tumor metastatic potential. The up-regulation of miR-375 suppressed colorectal cancer cell migration and invasion in vitro and reduced tumor metastases in murine models established by both orthotopic implantation and spleen injection. Furthermore, we identified Frizzled 8 (FZD8) as a direct target of miR-375 in CRC, and miR-375 negatively regulated Wnt/β-catenin signaling by suppressing FZD8. More importantly, FZD8 expression inversely correlated with overall survival in human CRC patients and is a likely independent predictor of survival. Therefore, we concluded that miR-375 functions as a tumor-suppressive microRNA by directly acting upon FZD8, which may serve as a new therapeutic target to inhibit tumor metastasis in CRC.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-375 suppresses human colorectal cancer metastasis by targeting Frizzled 8

Wen

Liu

et al. 2016

Oncotarget

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“…De-regulation of miRNA, such as miR-21, miR-22, miR-448, miR-654-3p, miR-205, miR-216a, miR-143, and miR-181a in NSCLC is a key factor underlying tumorigenesis (Wang et al, 2014;Xu et al, 2015). Human miR-204 is down-regulated in several tumor types, including NSCLC Shi et al, 2014;Xia et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…For example,, and miR-125a-5p expression is associated with the progression and prognosis of non-small cell lung cancer (Kim et al, 2014;Zhu et al, 2014). miR125b, an oncogenic miRNA, is upregulated in lung cancer, and has been reported to promote cancer progression (Wang et al, 2015), whereas miR-216a, miR-27b, miR-338-3p, miR-30, and miR-99a, which function as tumor-suppressors, are down-regulated in breast cancer cells Jiang et al, 2014;Wang et al, 2014;Zhong et al, 2014;Chen et al, 2015). Recent studies have shown that some miRNA function as a tumor suppressors in NSCLC (Xia et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

miR-204 suppresses non-small-cell lung carcinoma (NSCLC) invasion and migration by targeting JAK2

Wang

Lv²,

Zhou

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Aberrant expression of microRNA is associated with the development and progression of cancers. down-regulation has been previously demonstrated in non-small-cell lung carcinoma (NSCLC); however, the underlying mechanism by which miR-204 suppresses tumorigenesis in NSCLC remains elusive. In this study, miR-204 expression was found to be down-regulated, and that of Janus kinase 2 (JAK2) was found to be up-regulated in four NSCLC cell lines (A549, H1299, H1650, and H358) compared to the normal lung cell line. The overexpression of miR-204 suppressed the invasive and migratory capacities of H1299 cells. A luciferase assay confirmed that the binding of miR-124 to the -untranslated region of JAK2 inhibited the expression of JAK2 proteins in H1299 cells. JAK-2 overexpression effectively reversed miR-204-repressed NSCLC metastasis. Taken together, our findings revealed that miR-204 functions as a tumor suppressor in NSCLC by targeting JAK2, and that miR-204 may therefore serve as a biomarker for the diagnosis and treatment of NSCLC.

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“…Small ncRNAs, including microRNAs, have been demonstrated to function primarily via regulating gene expression, including modulating mRNA stability and repressing protein translation [9]. A number of microRNAs were found to act as oncogenes or tumor suppressor genes by previous reports [10–12]. Characterized by lack of cross species conservation [13, 14], the mechanism of action for long ncRNAs (lncRNAs) is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

The lncRNA CRNDE promotes colorectal cancer cell proliferation and chemoresistance via miR-181a-5p-mediated regulation of Wnt/β-catenin signaling

et al. 2017

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BackgroundWith more than 600,000 mortalities each year, colorectal cancer (CRC) is the third most commonly diagnosed type of cancer worldwide. Recently, mechanisms involving noncoding RNAs have been implicated in the development of CRC.MethodsWe examined expression levels of lncRNA CRNDE and miR-181a-5p in 64 cases of CRC tissues and cell lines by qRT-PCR. Gain-of-function and loss-of-function assays were performed to examine the effect of CRNDE and miR-181a-5p on proliferation and chemoresistance of CRC cells. Using fluorescence reporter and western blot assays, we also explored the possible mechanisms of CRNDE in CRC cells.ResultsIn this study, we found that the expression levels of the CRNDE were upregulated in CRC clinical tissue samples. We identified microRNA miR-181a-5p as an inhibitory target of CRNDE. Both CRNDE knockdown and miR-181a-5p overexpression in CRC cell lines led to inhibited cell proliferation and reduced chemoresistance. We also determined that β-catenin and TCF4 were inhibitory targets of miR-181a-5p, and that Wnt/β-catenin signaling was inhibited by both CRNDE knockdown and miR-181a-5p overexpression. Significantly, we found that the repression of cell proliferation, the reduction of chemoresistance, and the inhibition of Wnt/β-catenin signaling induced by CRNDE knockdown would require the increased expression of miR-181a-5p.ConclusionsOur study demonstrated that the lncRNA CRNDE could regulate the progression and chemoresistance of CRC via modulating the expression levels of miR-181a-5p and the activity of Wnt/β-catenin signaling.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0583-1) contains supplementary material, which is available to authorized users.

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Decreased Expression of miR216a Contributes to Non–Small-Cell Lung Cancer Progression

Cited by 52 publications

References 38 publications

MicroRNA-375 suppresses human colorectal cancer metastasis by targeting Frizzled 8

MicroRNA-375 suppresses human colorectal cancer metastasis by targeting Frizzled 8

miR-204 suppresses non-small-cell lung carcinoma (NSCLC) invasion and migration by targeting JAK2

The lncRNA CRNDE promotes colorectal cancer cell proliferation and chemoresistance via miR-181a-5p-mediated regulation of Wnt/β-catenin signaling

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