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Junctional adhesion molecule (JAM) family
Published in C. Yan Cheng, Spermatogenesis, 2018
MicroRNAs (miRNAs) are small noncoding RNAs that control gene expression at both transcriptional and translational levels and have been identified to regulate the expression of JAMs. For instance, in breast cancer, miR-145 is downregulated and miR-495 is upregulated and they both target JAM-A.71,72 Overexpression of miR-145 downregulates JAM-A and causes the restructuring of the actin cytoskeleton, resulting in decreased motility and invasiveness,71 while inhibition of JAM-A by miR-495 promotes breast cancer cell migration.72 Efforts should be made to examine if JAMs and CAR in the testis can be regulated by miRNA.
Molecular diagnosis of endometriosis
Published in Carlos Simón, Linda C. Giudice, The Endometrial Factor, 2017
Lusine Aghajanova, Linda C. Giudice
Paired analysis of eutopic and ectopic endometrium has demonstrated differential expression of miRNAs in these tissues (88,90). Downregulation of miR-196b in ectopic endometriotic tissue was consistently demonstrated, and its overexpression inhibits cell proliferation and induces apoptosis in endometriotic cells (90,91). Global miRNA array analysis of eutopic endometrium from women with and without endometriosis revealed significant downregulation of members of the miR-9 and miR-34 families in ESE from women with endometriosis, associated with the biological processes of cell death, cell cycle, and cellular assembly and organization (92). Laudanski et al. (93) found miR-483-5p and miR-629* to be downregulated in eutopic endometrium from women with endometriomas (93) (Table 4.2). Joshi et al. (94) demonstrated significant downregulation of miR-451 in eutopic endometrium from women with endometriosis compared with no-disease controls and baboons before and 3 months after induction of endometriosis. Overexpression of miR-145 correlated with decreased cell proliferation (94). Peritoneal fluid from subjects with endometriosis has been shown to modify miRNA profiles of eutopic endometrial stromal cells in vitro (95).
Great strides in precision medicine: Personalized oncology and molecular diagnostics
Published in Priya Hays, Advancing Healthcare Through Personalized Medicine, 2017
The microRNA (miRNA) paradigm shifted from worm development to cancer when G.A. Calin et al. identified miR-15 and miR-16 as tumor suppressors in chronic lymphocytic leukemia in 2002. Fifty percent of CLL and MCL patients have homozygous loss of this genetic region (13q14), and 68% of patients do not express miR-15 and 16. Shortly after, Michael et al. (2003) showed a similarly reduced expression of mature miR-143 and miR-145 in CRC. In Takamizawa et al., 2004, showed that let-7 was often lost in lung cancer. These landmark studies established the importance of miRNAs in cancer.
Diagnostic value of non-coding RNAs in ovarian cancer
Published in Journal of Obstetrics and Gynaecology, 2022
Ningxia Sun, Shiguo Liu, Aiping Chen
Studies have found that circRNAs can also act as competing endogenous RNAs (ceRNAs), bind to miRNAs, and act as miRNA sponges in cells, changing the expression levels of downstream target genes, before regulating the effect of miRNAs. circ-ITCH is down-regulated in a variety of cancers and acts as a powerful tumour suppressor through competing endogenous RNA (ceRNA) pathways. miR-145, as a tumour suppressor gene, is involved in regulating the growth, proliferation, and metastasis of tumour cells (Xu et al. 2019). Hu et al. (2018a) reported for the first time that circ-ITCH, acting as ceRNA on miR-145 in ovarian cancer tissues and cells, increases the level of RASA1, and inhibits the malignant progression of OC in vivo and in vitro through the circ-ITCH-miR-145-RASA1 axis. It provides a new target for the treatment of malignant tumours. Circ-WHSC1 also acts on miR-145 and upregulates the expression of downstream target genes MUC1 and hTERT, and acts on peritoneal mesenchymal cells in the form of exosomes to induce tumour metastasis (Zong et al. 2019). In addition to miR145, miR-1182 is also inhibited by circWHSC1, weakening the synergistic effect of miR-1182 and miR-145, and limiting the inhibitory effect of both simultaneously, thus enabling the rapid development of ovarian cancer tissues and cells. Although the current reports on the interaction between circRNA and miRNA are not as mature as lncRNA, new understandings have been gained on the mechanism of circRNA acting as a molecular sponge of miRNA. Figure 2 shows the network of interactions between different ncRNAs.
Alternative therapeutic strategy for existing aortic aneurysms using mesenchymal stem cell–derived exosomes
Published in Expert Opinion on Biological Therapy, 2022
Motoshi Kozakai, Yuji Narita, Aika Yamawaki-Ogata, Kazuro L Fujimoto, Masato Mutsuga, Yoshiyuki Tokuda, Akihiko Usui
Spinosa and colleagues have reported that MSC-derived EVs attenuate abdominal AA formation and mitigate pro-inflammatory cytokine production and inflammatory cell infiltration via miR-147 in an elastase-treated murine model [32]. We investigated the distribution of miRs in MSC-exs. We detected expression of 537 different miRs, but miR-147 was not detected. This could be due to MSC characteristics [33]. The origin of the MSCs used in each study varied. MSCs were derived from murine bone marrow in our study whereas Spinosa et al. used human umbilical cord-derived MSCs isolated from Wharton’s jelly. Regarding the therapeutic effects of miRs detected in our MSC-exs, the expression levels of 6 miRs that induce AA formation were low and the expression levels of 10 miRs that inhibit AA formation were high. Among these 10 miRs, the miR-23/24/27 family mediates angiogenesis and arteriogenesis, miR-21 and miR-221 regulate anti-apoptotic effects in SMCs, miR-143 and miR-145 regulate SMC differentiation and phenotype, and miR-92 regulates neovascularization [34–36]. Thus, these miRs, except for miR-147, might mediate the therapeutic effects of MSC-exs in AAs.
Geniposide protects PC12 cells from lipopolysaccharide-evoked inflammatory injury via up-regulation of miR-145-5p
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Shaolong Ma, Chao Zhang, Ziyan Zhang, Yuxuan Dai, Rui Gu, Rui Jiang
microRNAs (miRNAs) are a sort of non-protein coding RNAs that play momentous roles in the pathology of almost all human diseases including SCI [13]. Besides this, multiple literature recognized miRNAs as major targets of traditional Chinese medicines in exerting their beneficial functions [14,15]. miR-145-5p has long been known as a tumour suppressor that its expression is frequently down-regulated in human cancers [16,17]. Apart from the anti-tumour role, miR-145-5p was also found to be implicated in other diseases including SCI. As reported by Wang et al., miR-145-5p was enriched in rat spinal neurons and astrocytes and was low expressed following SCI [18]. A later literature confirmed the down-regulated miR-145-5p in SCI rats and further revealed its down-regulation altered myostatin signalling paralyzed by motor neuron injuries [19]. Therefore, whether miR-145-5p was an effector miRNA of geniposide was explored in this study, to provide a possible explanation of geniposide’s beneficial effect.