Characterization of placenta‐specific microRNAs in fetal growth restriction pregnancy

Higashijima, Ai; Miura, Kiyonori; Mishima, Hiroyuki; Kinoshita, Akira; Jo, Ozora; Abe, Shuhei; Hasegawa, Yoshihiro; Miura, Shoko; Yamasaki, Kentaro; Yoshida, Atsumi; Yoshiura, Koh-ichiro; Masuzaki, Hiroaki

doi:10.1002/pd.4045

Cited by 135 publications

(126 citation statements)

References 36 publications

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“…miR‐515‐5p was initially described to be a placenta‐specific miRNA involved in foetal growth 10. However, recently, we identified its role as a tumour suppressor in breast cancer 11.…”

Section: Introductionmentioning

confidence: 99%

miR‐515‐5p controls cancer cell migration throughMARK4 regulation

et al. 2016

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Here, we show that miR‐515‐5p inhibits cancer cell migration and metastasis. RNA‐seq analyses of both oestrogen receptor receptor‐positive and receptor‐negative breast cancer cells overexpressing miR‐515‐5p reveal down‐regulation of NRAS, FZD4, CDC42BPA, PIK3C2B and MARK4 mRNAs. We demonstrate that miR‐515‐5p inhibits MARK4 directly 3′ UTR interaction and that MARK4 knock‐down mimics the effect of miR‐515‐5p on breast and lung cancer cell migration. MARK4 overexpression rescues the inhibitory effects of miR‐515‐5p, suggesting miR‐515‐5p mediates this process through MARK4 down‐regulation. Furthermore, miR‐515‐5p expression is reduced in metastases compared to primary tumours derived from both in vivo xenografts and samples from patients with breast cancer. Conversely, miR‐515‐5p overexpression prevents tumour cell dissemination in a mouse metastatic model. Moreover, high miR‐515‐5p and low MARK4 expression correlate with increased breast and lung cancer patients' survival, respectively. Taken together, these data demonstrate the importance of miR‐515‐5p/MARK4 regulation in cell migration and metastasis across two common cancers.

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Section: Introductionmentioning

confidence: 99%

miR‐515‐5p controls cancer cell migration throughMARK4 regulation

et al. 2016

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“…Many studies have investigated miRNA regulation of gene expression in the context of various pathologies, particularly those affecting humans. These include fetal weight restriction and low fetal birth weight (intrauterine growth retardation or IUGR), [81][82][83][84] toxin exposures such as environmental toxins, 85,86 cancer (hepatocellular carcinoma), 87 diabetes mellitus 88 and, the most heavily studied, human pre-eclampsia. 79,[89][90][91][92][93][94][95][96] Many of the pre-eclampsia studies have investigated miRNA expression using high throughput microarray, and qPCR (primarily in order to validate specific microarray findings).…”

Section: Microrna Regulation In the Placentamentioning

confidence: 99%

MicroRNAs, immune cells and pregnancy

et al. 2014

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MicroRNAs (miRNAs) are a recently discovered class of non-coding RNAs that are expressed in many cell types, where they regulate the expression of complementary RNAs, thus modulating the stability and translation of mRNAs. miRNAs are predicted to regulate the expression of ,50% of all protein coding genes in mammals. Therefore, they participate in virtually all cellular processes investigated so far. Altered miRNAs expressions are associated with both physiological (pregnancy) and pathological processes (cancer). As the dynamic maternal-fetal interface plays a critical role in the maintenance of successful pregnancy, it is not surprising that the miRNAs that are unique to reproductive tissues are abundantly expressed. Research in this field has demonstrated the presence and dysregulation of a distinct set of pregnancy-associated miRNAs; however, most studies have centered on localizing various miRNAs in reproductive microdomains associated with normal or complicated pregnancies. Although several independent miRNA regulatory mechanisms associated with endometrial receptivity, immune cells, angiogenesis and placental development have been studied, miRNA-mediated regulation of pregnancy remains poorly understood. This review provides a summary of the current data on miRNA regulation as well as functional profiles of miRNAs that are found in the uterus, in immune cells associated with maternal tolerance to the fetus, and those involved in angiogenesis and placental development.

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“…There were no significant differences between the CHM and control groups in maternal age or gestational age (data not shown). Preparation and extraction of total RNA containing small RNA molecules from tissue samples or from 1.2-mL samples of cell-free plasma, as well as absolute RT-qPCR analysis, were performed as described previously (1,2 ). The intraassay CVs for hsamiR-520b, -miR-520f, and -520c-3p) in the absolute RT-qPCR assays were 8.1%, 6.4%, and 6.8%, respectively.…”

Section: Identification Of Complete Hydatidiform Mole Pregnancy-assocmentioning

confidence: 99%

“…Isolation of total RNA (including small RNAs), assessment of their quality, concentration measurements, construction of a small-RNA library, next-generation sequencing (NGS), miRNA mapping, and NGS analysis of the differential expression of miRNA-encoding genes were performed as described previously (2 ) To compare miRNA concentrations across the data set, we corrected the sequencing bias of GC content for each miRNA (3 ) and normalized the sequencing read count as reads per kilobase of exon model per million mapped reads (RPKM) (4 ). NGS analysis of the sample set detected 503 miRNAs in CHM tissue, 497 miRNAs in the patient's blood cells, and 715 miRNAs in normal villous tissue.…”

Section: Identification Of Complete Hydatidiform Mole Pregnancy-assocmentioning

confidence: 99%