MicroRNAs (miRNAs) are a group of noncoding RNA molecules of 20-23 nucleotides length that negatively regulate gene expressions in numerous cellular processes. Through complementary paring with target mRNAs, miRNAs have frequently emerged as dual regulators of cancer development by acting on multiple signaling pathways, thereby act as novel biomarkers for cancer diagnosis, prognosis, and prediction of response to treatment. As one of them, miR-30a has been found to act as an onco-suppressor of tumorigenesis pathways through inhibition of cellular proliferation, migration and invasion. Simultaneously, miR-30a plays a progressing role in several types of cancer, determined by relevant target genes as well. In the present review, we summarize recent research regarding miR-30a, including its biological function, expression and regulation, especially focusing on its role in cancer development and progression. Clinically, miR-30a may serve as a potential target in the diagnosis and therapy of human cancer.

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The Versatile Role of microRNA-30a in Human Cancer

Preeclampsia (PE) is an often fatal pathology characterized by hypertension and proteinuria at the 20th week of gestation that affects 5-10% of the pregnancies. The problem is particularly important in developing countries in where the incidence of hypertensive disorders of pregnancy is higher and maternal mortality rates are 20 times higher than those reported in developed countries. Risk factors for the development of PE include obesity, insulin resistance and hyperlipidemia that stimulate inflammatory cytokine release and oxidative stress leading to endothelial dysfunction (ED). However, how all these clinical manifestations concur to develop PE is still not very well understood. The related poor trophoblast invasion and uteroplacental artery remodeling described in PE, increases reactive oxygen species (ROS), hypoxia and ED. Here we aim to review current literature from research showing the interplay between oxidative stress, ED and PE to the outcomes of current clinical trials aiming to prevent PE with antioxidant supplementation.

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Endothelial dysfunction and preeclampsia: role of oxidative stress

Metformin, the aspirin of the 21st century: its role in gestational diabetes mellitus, prevention of preeclampsia and cancer, and the promotion of longevity.

Proper placental development and function are central to the health of both the mother and the fetus during pregnancy. A critical component of healthy placental function is the proper development of its vascular network. Poor vascularization of the placenta can lead to fetal growth restriction, preeclampsia, and in some cases fetal death. Therefore, understanding the mechanisms by which uterine stressors influence the development of the placental vasculature and contribute to placental dysfunction is of central importance to ensuring a healthy pregnancy. In this review we discuss how oxidative stress observed in maternal smoking, maternal obesity, and preeclampsia has been associated with aberrant angiogenesis and placental dysfunction resulting in adverse pregnancy outcomes. We also highlight that oxidative stress can influence the expression of a number of transcription factors important in mediating angiogenesis. Therefore, understanding how oxidative stress affects redox-sensitive transcription factors within the placenta may elucidate potential therapeutic targets for correcting abnormal placental angiogenesis and function.

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Angiogenesis in the placenta: the role of reactive oxygen species signaling.

https://espace.library.uq.edu.au/view/UQ:428520/UQ428520_OA.pdf

Review: Placental mitochondrial function and structure in gestational disorders.

Background: Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women of reproductive age, is characterized by polycystic ovaries, chronic anovulation, hyperandrogenism and insulin resistance. Despite the high prevalence of hyperandrogenemia, a definitive endocrine marker for PCOS has so far not been identified. Circulating miRNAs have recently been shown to serve as diagnostic/prognostic biomarkers in patients with cancers. Our current study focused on the altered expression of serum miRNAs and their correlation with PCOS. Method and Results: We systematically used the TaqMan Low Density Array followed by individual quantitative reverse transcription polymerase chain reaction assays to identify and validate the expression of serum miRNAs of PCOS patients. The expression levels of three miRNAs (miR-222, miR-146a and miR-30c) were significantly increased in PCOS patients with respect to the controls in our discovery evaluation and followed validation. The area under the receiver operating characteristic (ROC) curve (AUC) is 0.799, 0.706, and 0.688, respectively. The combination of the three miRNAs using multiple logistic regression analysis showed a larger AUC (0.852) that was more efficient for the diagnosis of PCOS. In addition, logistic binary regression analyses show miR-222 is positively associated with serum insulin, while miR-146a is negatively associated with serum testosterone. Furthermore, bioinformatics analysis indicated that the predicted targets function of the three miRNAs mainly involved in the metastasis, cell cycle, apoptosis and endocrine. Conclusion: Serum miRNAs are differentially expressed between PCOS patients and controls. We identified and validated a class of three serum miRNAs that could act as novel non-invasive biomarkers for diagnosis of PCOS. These miRNAs may be involved in the pathogenesis of PCOS.

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Characterization of serum microRNAs profile of PCOS and identification of novel non-invasive biomarkers.

Introduction 
Pre-eclampsia (PE), a severe pregnancy-specific disease characterized by the new onset of hypertension, proteinuria, edema, and a series of other systematic disorders, is a state of widespread mitochondrial dysfunction of the placenta.
Methods 
We compared the morphology of mitochondria in pre-eclamptic and normotensive placentae using electron microscopy. To reveal the systematic protein expression changes of placental mitochondria that might explain the pathogenesis of PE, we performed iTRAQ analysis combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) on differentially expressed placental mitochondria proteins from 4 normotensive and 4 pre-eclamptic pregnancies. Bioinformatics analysis was used to find the relative processes that these differentially expressed proteins were involved in. Three differentially expressed proteins were chosen to confirm by Western blotting and immunohistochemistry.
Results 
Morphological data demonstrated degenerative and apoptotic changes in the mitochondria of pre-eclamptic placentae. We found four proteins were upregulated and 22 proteins were downregulated in pre-eclamptic placentae compared with normotensive placentae. Bioinformatics analysis showed that these proteins were involved in many critical processes in the development of pre-eclampsia such as apoptosis, fatty acid oxidation, the respiratory chain, reactive oxygen species generation, the tricarboxylic acid cycle and oxidative stress.
Conclusions 
This preliminary work provides a better understanding of the proteomic alterations of mitochondria from pre-eclamptic placentae and may aid in our understanding of the importance of mitochondria in the development of pre-eclampsia.

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Comparative Proteomics Analysis Suggests that Placental Mitochondria are Involved in the Development of Pre-Eclampsia

// Xuejing Song 1, 2, * , Can Rui 1, * , Li Meng 3 , Rui Zhang 1 , Rong Shen 3 , Hongjuan Ding 1 , Jun Li 4 , Jingyun Li 4 , Wei Long 1 1 Department of Obstetrics, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China 2 Fourth Clinical Medicine College, Nanjing Medical University, Nanjing, China 3 Nanjing Maternity and Child Health Medical Institute, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China 4 State key Laboratory of Reproductive Medicine, Department of Plastic and Cosmetic Surgery, Maternal and Child Health Medical Institute, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China * These authors contributed equally to this work Correspondence to: Wei Long, email: wlong@njmu.edu.cn Jingyun Li, email: dagumahao@163.com Keywords: lncRNA, RPAIN, early onset preeclampsia, complement protein C1q Received: October 09, 2016      Accepted: December 01, 2016      Published: December 09, 2016 ABSTRACT Long non-coding RNAs (lncRNAs) are key regulatory molecules that are involved in a variety of biological processes and human diseases. Their impact on early onset preeclampsia remains unclear. In this study, we tested the expression of RPAIN (transcript variant 12 of RPA interacting protein, a non-coding RNA, NR_027683.1) in placenta tissues derived from 25 pregnant women with PE and 15 healthy pregnant women using quantitative real-time PCR. The effect of RPAIN on trophoblast proliferation, invasion, and apoptosis and the underlying mechanisms were examined in trophoblast cell lines (HTR-8/SVneo). The results showed that RPAIN expression levels were significantly increased in early onset preeclamptic placentas compared to normal controls. The proliferation and invasive abilities of the trophoblast cells were significantly inhibited, and the apoptosis abilities of the trophoblast cells were significantly promoted when RPAIN was overexpressed. In addition, the overexpression of RPAIN inhibited the expression of complement protein C1q. Furthermore, C1q overexpression rescued the decreased cell invasion and enhanced cell apoptosis in RPAIN-overexpressing trophoblast cells. Our results suggest that increased RPAIN levels may contribute to the development of preeclampsia through regulating trophoblast invasion and apoptosis via C1q. Therefore, we proposed RPAIN as a novel lncRNA molecule, which might contribute to the development of PE (preeclampsia) and might compose a potential diagnostic and therapeutic target for this disease.

/pdf/long-non-coding-rna-rpain-regulates-the-invasion-and-19rst2vp0b.pdf

Long non-coding RNA RPAIN regulates the invasion and apoptosis of trophoblast cell lines via complement protein C1q.

Distinct expression profiles of lncRNAs between early-onset preeclampsia and preterm controls.

Background: Fetal macrosomia and its associated complications are the most frequent and serious morbidities for infants associated with gestational diabetes mellitus (GDM) The associations between long non-coding RNAs (lncRNAs) and macrosomia have been rarely reported; therefore, we investigated the umbilical cord lncRNA profiles in GDM macrosomia Method: Thirty pairs of GDM macrosomia and normal controls were divided into three subgroups randomly, and the umbilical cord vein blood from each subgroup was mixed, and hybridized to a microarray containing probes representing 33,000 lncRNA genes Quantitative real-time polymerase chain reaction (qPCR) was used to validate selected differentially expressed lncRNAs The gene ontology (GO), pathway and network analysis were performed Result: The microarray identified 8814 lncRNAs that were expressed in the umbilical cord blood, of which 349 were significantly upregulated and 892 were significantly downregulated (fold-change ≥ 20) in GDM group The highest enriched GOs targeted by downregulated transcripts were biological regulation Pathway analysis indicated that nine pathways corresponded to downregulated transcripts Conclusions: Certain lncRNAs that were aberrantly expressed in the umbilical cord blood from GDM macrosomia might play a partial or key role in GDM macrosomia development This study provided potential targets for treatment of macrosomia and novel insights into macrosomia biology

/pdf/microarray-expression-profile-analysis-of-long-non-coding-3v21vdkpcs.pdf

Microarray Expression Profile Analysis of Long Non-Coding RNAs in Umbilical Cord Plasma Reveals their Potential Role in Gestational Diabetes-Induced Macrosomia

Wei Long

Papers

Characterization of serum microRNAs profile of PCOS and identification of novel non-invasive biomarkers.

Comparative Proteomics Analysis Suggests that Placental Mitochondria are Involved in the Development of Pre-Eclampsia

Long non-coding RNA RPAIN regulates the invasion and apoptosis of trophoblast cell lines via complement protein C1q.

Distinct expression profiles of lncRNAs between early-onset preeclampsia and preterm controls.

Microarray Expression Profile Analysis of Long Non-Coding RNAs in Umbilical Cord Plasma Reveals their Potential Role in Gestational Diabetes-Induced Macrosomia