The expression of the let-7 miRNAs and Lin28 signalling pathway in human term gestational tissues

Chan, Hsiu‐Wen; Lappas, Martha; Yee, Sarah; Vaswani, Kanchan; Mitchell, Murray D.; Rice, Gregory E.

doi:10.1016/j.placenta.2013.02.008

Cited by 28 publications

(29 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Like miR-125b, let-7 miRNAs, including let-7c were upregulated in third trimester human placentas compared to the first trimester [22]. In support of our results, another study found tissue-specific let-7c expression differences at term, with significantly reduced expression in choriodecidua as compared to amnion and placenta [33]. …”

Section: Discussionsupporting

confidence: 85%

Expression patterns of the chromosome 21 MicroRNA cluster (miR-99a, miR-125b and let-7c) in chorioamniotic membranes

et al. 2017

View full text Add to dashboard Cite

Trisomy 21 (T21) is the most common chromosome abnormality in humans and is associated with a spectrum of phenotypes, including cognitive impairment, congenital heart defects and immune system defects. In addition, T21 is also associated with abnormalities of fetal membranes including chorioamniotic separation, delayed fusion of the chorioamniotic membranes, defects in syncytiotrophoblast formation, as well as amniocyte senescence. There is evidence indicating miRNAs encoded by sequences on chromosome 21 (Chr-21) are involved in several of the cognitive and neurological phenotypes of T21, but the role of Chr- 21 derived miRNAs in fetal membrane abnormalities associated with T21 has not been investigated. In the current study, we determined the expression patterns of three miRNAs derived from a cluster on Chr-21 - hsa-miR-99a, hsa-miR-125b and hsa-let-7c in chorioamniotic membranes obtained from term pregnancies with spontaneous rupture (n = 20). Tissue and location specific expression patterns within the chorioamniotic membranes were identified. The rupture zone in the choriodecidua had distinct expression patterns compared to other fetal membrane locations. Despite the increased gene dosage associated with T21, the expression of all three miRNAs was reduced in cultured T21 amniocytes as compared to cultured euploid amniocytes. In silico analysis of experimentally validated targets of the three miRNAs suggest these Chr-21 derived miRNAs play a potential role in fetal membrane rupture and the fetal membrane defects associated with T21.1

show abstract

Section: Discussionsupporting

confidence: 85%

Expression patterns of the chromosome 21 MicroRNA cluster (miR-99a, miR-125b and let-7c) in chorioamniotic membranes

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Indeed, lung irradiation induces the expression of pro-inflammatory cytokines; for example, interleukin (IL-6) levels were significantly higher during and after thoracic irradiation therapy in lung cancer patients who developed RP [30, 31], whereas let-7 miRNA overexpression significantly reduced IL-6 expression. Recently, some published studies have indicated that LIN28 links inflammation to cell transformation [13, 14], LIN28B functions as a post-transcriptional regulator of let-7 miRNA biogenesis by inhibiting the microprocessor-mediated cleavage of pri-let-7 miRNAs [12], and NF-kB activates LIN28B and inhibits let-7 miRNA expression, leading to overexpression of IL-6 by NF-kB activation [13–15]. It is well known that LIN28B is a homologue of LIN28A [20], and both LIN28A and LIN28B also pay an important role during multiple cellular development processes and tumorigenesis in humans.…”

Section: Discussionmentioning

confidence: 99%

“…Although the inflammation mechanism of Lin28 is still largely unknown, it is believed that LIN28B plays a key role in regulation of inflammation by regulating IL-6 expression. Indeed, it has been identified that the nuclear factor-kB (NF-kB) regulates the expression of a wide range of genes involved in inflammation and that NF-kB activates LIN28B but inhibits let-7 miRNA expression, resulting in higher levels of IL-6 by NF-kB activation [13–15]. …”

Section: Introductionmentioning

confidence: 99%

Genetic variants of the LIN28B gene predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy

Jiang

Liu

Wang

et al. 2014

European Journal of Cancer

View full text Add to dashboard Cite

Background LIN28 is an RNA-binding protein that not only plays key roles in multiple cellular developmental processes and tumorigenesis, but also is involved in tissue inflammatory response. However, no published study has investigated associations between genetic variants in LIN28 and radiation-induced pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) treated with definitive radiation therapy. Methods We genotyped eight potentially functional single nucleotide polymorphisms (SNPs) of LIN28A (rs11247946 T>C, rs3811464 C>T, rs11581746 T>C, and rs12728900 G>A), and LIN28B (rs314280 A>G, rs12194974 G>A, rs17065417 A>C and rs314276 C>A) in 362 patients with NSCLC, who received definitive radio (chemo) therapy. The associations between RP risk and genotypes were assessed by hazards ratio (HR) in Cox proportional hazards regression analysis with time to event considered with and without adjustment for potential confounders. Results Multivariate analyses found that patients carrying LIN28B rs314280 AG and AA/AG or rs314276 AC and AA/AC genotypes had a higher risk of grade ≥3 RP (for rs314280 AG and AA/AG versus GG, adjusted HR= 2.97 and 2.23, 95% CI, 1.32–6.72 and 1.01–4.94, P = 0.009 and 0.048, respectively; for rs314276 AC and AA/AC versus CC, adjusted HR = 2.30 and 2.00, 95% CI, 1.24–4.28 and 1.11–3.62, and P = 0.008 and 0.022, respectively). Further stratified analyses showed a more profound risk in the subgroups of the age <65 years subjects, males, stage III/IV, ever smokers and MLD ≥19.0 Gy. Conclusion Genetic variants of LIN28B, but not LIN28A, may be biomarkers for susceptibility to severe RP in NSCLC patients. Large, prospective studies are needed to confirm our findings.

show abstract

“…Let-7 functions downstream of NF- κ B signaling pathway and negatively regulates IL-6 expression. Strong expression of let-7 was detected in the placenta and amnion, implying the possible regulation on placental inflammation [36]. Similarly, miR-181a blocks the activation of TGF- β signaling pathway and enhances expression of IL-6; thus increased expression of miR-181a in the placenta attenuates the immunosuppressive properties of mesenchymal stem cells and contributes to the abnormal pregnancy [63].…”

Section: Placental Micrornamentioning

confidence: 99%

Small Molecule, Big Prospects: MicroRNA in Pregnancy and Its Complications

Cai

Kolluru

Ahmed

2017

Journal of Pregnancy

View full text Add to dashboard Cite

MicroRNAs are small, noncoding RNA molecules that regulate target gene expression in the posttranscriptional level. Unlike siRNA, microRNAs are “fine-tuners” rather than “switches” in the regulation of gene expression; thus they play key roles in maintaining tissue homeostasis. The aberrant microRNA expression is implicated in the disease process. To date, numerous studies have demonstrated the regulatory roles of microRNAs in various pathophysiological conditions. In contrast, the study of microRNA in pregnancy and its associated complications, such as preeclampsia (PE), fetal growth restriction (FGR), and preterm labor, is a young field. Over the last decade, the knowledge of pregnancy-related microRNAs has increased and the molecular mechanisms by which microRNAs regulate pregnancy or its associated complications are emerging. In this review, we focus on the recent advances in the research of pregnancy-related microRNAs, especially their function in pregnancy-associated complications and the potential clinical applications. Here microRNAs that associate with pregnancy are classified as placenta-specific, placenta-associated, placenta-derived circulating, and uterine microRNA according to their localization and origin. MicroRNAs offer a great potential for developing diagnostic and therapeutic targets in pregnancy-related disorders.

show abstract

The expression of the let-7 miRNAs and Lin28 signalling pathway in human term gestational tissues

Cited by 28 publications

References 37 publications

Expression patterns of the chromosome 21 MicroRNA cluster (miR-99a, miR-125b and let-7c) in chorioamniotic membranes

Expression patterns of the chromosome 21 MicroRNA cluster (miR-99a, miR-125b and let-7c) in chorioamniotic membranes

Genetic variants of the LIN28B gene predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy

Small Molecule, Big Prospects: MicroRNA in Pregnancy and Its Complications

Contact Info

Product

Resources

About