MicroRNA expression signature of oral squamous cell carcinoma: functional role of microRNA-26a/b in the modulation of novel cancer pathways

Fukumoto, Ichiro; Hanazawa, Toyoyuki; Kinoshita, Takashi; Kikkawa, Naoko; Koshizuka, Keiichi; Goto, Yusuke; Nishikawa, Rika; Chiyomaru, Takeshi; Enokida, Hideki; Nakagawa, Masayuki; Okamoto, Yoshitaka; Seki, Naohiko

doi:10.1038/bjc.2015.19

Cited by 108 publications

(107 citation statements)

References 41 publications

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“…MiR-26b also displayed low levels of expression in a human embryonic stem cell line (HUES-17) and in a colorectal cancer cell line with a high metastatic potential (LoVo) [64]. Loss of miR-26b also enhanced migration and invasion in oral squamous cell carcinoma [65]. Additionally, miR-26b expression in neural stem cells was found to be induced during their differentiation into neurons in vivo [66].…”

Section: Discussionmentioning

confidence: 99%

Identification of microRNA profile specific to cancer stem-like cells directly isolated from human larynx cancer specimens

et al. 2016

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BackgroundEmerging evidences proposed that microRNAs are associated with regulation of distinct physio-pathological processes including development of normal stem cells and carcinogenesis. In this study we aimed to investigate microRNA profile of cancer stem-like cells (CSLCs) isolated form freshly resected larynx cancer (LCa) tissue samples.MethodsCD133 positive (CD133+) stem-like cells were isolated from freshly resected LCa tumor specimens. MicroRNA profile of 12 pair of CD133+ and CD133− cells was determined using microRNA microarray and differential expressions of selvected microRNAs were validated by quantitative real time PCR (qRT-PCR).ResultsMicroRNA profiling of CD133+ and CD133− LCa samples with microarray revealed that miR-26b, miR-203, miR-200c, and miR-363-3p were significantly downregulated and miR-1825 was upregulated in CD133+ larynx CSLCs. qRT-PCR analysis in a total of 25 CD133+/CD133− sample pairs confirmed the altered expressions of these five microRNAs. Expressions of miR-26b, miR-200c, and miR-203 were significantly correlated with miR-363-3p, miR-203, and miR-363-3p expressions, respectively. Furthermore, in silico analysis revealed that these microRNAs target both cancer and stem-cell associated signaling pathways.ConclusionsOur results showed that certain microRNAs in CD133+ cells could be used as cancer stem cell markers. Based on these results, we propose that this panel of microRNAs might carry crucial roles in LCa pathogenesis through regulating stem cell properties of tumor cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2863-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Identification of microRNA profile specific to cancer stem-like cells directly isolated from human larynx cancer specimens

et al. 2016

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“…The procedure for PCR quantification was previously described (13,18–20). The expression levels of miR-375 (assay ID: 000564; Applied Biosystems, Foster City, CA, USA) were analyzed by TaqMan qRT-PCR assays (TaqMan MicroRNA assays; Applied Biosystems) and RNU48 (assay ID: 001006) was used for normalization.…”

Section: Methodsmentioning

confidence: 99%

“…Currently, numerous studies have shown that miRNAs are aberrantly expressed in several cancers, including ESCC (6,8). Using miRNA expression signature analyses, we have sequentially identified tumor-suppressive miRNAs and shown that these miRNAs mediate novel cancer networks (9–13). …”

Section: Introductionmentioning

confidence: 99%

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Regulation of MMP13 by antitumor microRNA-375 markedly inhibits cancer cell migration and invasion in esophageal squamous cell carcinoma

Osako

Seki

Kita

et al. 2016

International Journal of Oncology

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Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies. Recently developed molecular targeted therapies are not available for patients with ESCC. After curative surgical resection, patients frequently suffer distant metastasis and recurrence. Exploration of novel ESCC metastatic pathways may lead to the development of new treatment protocols for this disease. Accordingly, we have sequentially identified microRNA (miRNA)-mediated metastatic pathways in several cancers. Our past studies of miRNA expression signatures have shown that microRNA-375 (miR-375) is frequently reduced in several types of cancers, including ESCC. In the present study, we aimed to investigate novel miR-375-mediated metastatic pathways in ESCC cells. The expression of miR-375 was downregulated in ESCC tissues, and ectopic expression of this miRNA markedly inhibited cancer cell migration and invasion, suggesting that miR-375 acted as an antimetastatic miRNA in ESCC cells. Our strategies for miRNA target searching demonstrated that matrix metalloproteinase 13 (MMP13) was directly regulated by miR-375 in ESCC cells. Overexpression of MMP13 was observed in ESCC clinical tissues, and the expression of MMP13 promoted cancer cell aggressiveness. Moreover, oncogenic genes, including CENPF, KIF14 and TOP2A, were shown to be regulated downstream of MMP13. Taken together, these findings demonstrated that the antitumor miR-375/oncogenic MMP13 axis had a pivotal role in ESCC aggressiveness. These results provide novel insights into the potential mechanisms of ESCC pathogenesis.

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“…[31][32][33][34] Our past study showed that downregulation of these miRNAs enhanced cancer cell migration and invasion in oral cancer through direct regulation of TMEM184B. 35 In PCa, EZH2, a histone-lysine N-methyltransferase enzyme, was directly regulated by miR-26a and miR-26b. 36 Overexpression of EZH2 is observed in several cancers and contributes to cancer aggressiveness.…”

Section: Discussionmentioning

confidence: 99%

Regulation of metastasis-promoting LOXL2 gene expression by antitumor microRNAs in prostate cancer

et al. 2016

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Our recent studies of microRNA (miRNA) expression signatures of prostate cancer (PCa) showed that six miRNAs (specifically, miR-26a, miR-26b, miR-29a, miR-29b, miR-29c and miR-218) were markedly reduced in cancer tissues. Moreover, ectopic expression of these miRNAs suppressed PCa cell aggressiveness, indicating that these miRNAs acted in concert to regulate genes that promoted metastasis. Genome-wide gene expression analysis and in silico database analysis identified a total of 35 candidate genes that promoted metastasis and were targeted by these 6 miRNAs. Using luciferase reporter assays, we showed that the lysyl oxidase-like 2 (LOXL2) gene was directly controlled by these tumor-suppressive miRNAs in PCa cells. Overexpression of LOXL2 was confirmed in PCa tissues and knockdown of the LOXL2 gene markedly inhibited the migration and invasion of PCa cells. Aberrant expression of LOXL2 enhanced migration and invasion of PCa cells. Downregulation of antitumor miRNAs might disrupt the tightly controlled RNA networks found in normal cells. New insights into the novel molecular mechanisms of PCa pathogenesis was revealed by antitumor miRNA-regulated RNA networks.

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MicroRNA expression signature of oral squamous cell carcinoma: functional role of microRNA-26a/b in the modulation of novel cancer pathways

Cited by 108 publications

References 41 publications

Identification of microRNA profile specific to cancer stem-like cells directly isolated from human larynx cancer specimens

Identification of microRNA profile specific to cancer stem-like cells directly isolated from human larynx cancer specimens

Regulation of MMP13 by antitumor microRNA-375 markedly inhibits cancer cell migration and invasion in esophageal squamous cell carcinoma

Regulation of metastasis-promoting LOXL2 gene expression by antitumor microRNAs in prostate cancer

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