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Long Non-Coding RNAs Serve as Diagnostic Biomarkers of Preeclampsia and Modulate Migration and Invasiveness of Trophoblast Cells.

ABSTRACT: BACKGROUND Long non-coding RNAs (lncRNAs) have emerged as crucial regulators of tumor progression. However, the effects of lncRNAs in preeclampsia are not entirely clear. The aim of this study was to demonstrate the potential of lncRNAs to serve as biomarkers in preeclampsia. MATERIAL AND METHODS The RNA expression levels of lncRNAs (NR_027457, BC030099, AF037219, NR_024178, AF085938, G43016, G36948, NR_029420, NR_024015, AK002210, NR_026643, and AL049277) in the serum of patients with preeclampsia and in the serum of normal controls were measured by qRT-PCR. The area under the curve (AUC), the optimal cut-off values, the specificity, and the sensitivity of NR_027457, AF085938, G36948, and AK002210 were analyzed by receiver operating characteristic (ROC) curve analysis. We designed RNA interference species to suppress NR_027457 and G36948 and identified the roles of NR_027457 and G36948 in the functions of a trophoblast cell line (HTR-8/SVneo). RESULTS The qRT-PCR results indicated that NR_027457 and AF085938 were significantly up-regulated, whereas G36948 and AK002210 were significantly down-regulated in preeclampsia. We found that NR_027457, AF085938, G36948, and AK002210 had potential diagnostic value for the detection of preeclampsia. Furthermore, the levels of NR_027457, AF085938, G36948, and AK002210 in the serum of patients were significantly different before vs. after surgery. The silencing of NR_027457 inhibited the proliferation, migration, and invasion abilities of HTR-8/SVneo cells, while the silencing of G36948 promoted the proliferation, migration, and invasion abilities of HTR-8/SVneo cells. CONCLUSIONS NR_027457, AF085938, G36948, and AK002210 can serve as potential diagnostic biomarkers in preeclampsia, and NR_027457 and G36948 might be involved in the pathogenesis of preeclampsia.

SUBMITTER: Luo X

PROVIDER: S-EPMC5766055 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Long Non-Coding RNAs Serve as Diagnostic Biomarkers of Preeclampsia and Modulate Migration and Invasiveness of Trophoblast Cells.

Luo Xiucui X Li Xiaoqiong X

Medical science monitor : international medical journal of experimental and clinical research 20180105

BACKGROUND Long non-coding RNAs (lncRNAs) have emerged as crucial regulators of tumor progression. However, the effects of lncRNAs in preeclampsia are not entirely clear. The aim of this study was to demonstrate the potential of lncRNAs to serve as biomarkers in preeclampsia. MATERIAL AND METHODS The RNA expression levels of lncRNAs (NR_027457, BC030099, AF037219, NR_024178, AF085938, G43016, G36948, NR_029420, NR_024015, AK002210, NR_026643, and AL049277) in the serum of patients with preeclamp ...[more]

PMID: 29302021

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Project description:Preeclampsia (PE) is a common cause of maternal morbidity, characterized by impaired trophoblast invasion and spiral artery transformation resulting in progressive uteroplacental hypoxia. Given the primary role of LIN28A and LIN28B in modulating cell metabolism, differentiation, and invasion, we hypothesized that LIN28A and/or LIN28B regulates trophoblast differentiation and invasion, and that its dysregulation may contribute to PE. Here we show that LIN28B is expressed ∼1300-fold higher than LIN28A in human term placenta and is the predominant paralog expressed in primary human trophoblast cultures. The expression of LIN28B mRNA and protein levels are significantly reduced in gestational age-matched preeclamptic vs. normal placentas, whereas LIN28A expression is not different. First trimester human placental sections displayed stronger LIN28B immunoreactivity in extravillous (invasive) cytotrophoblasts and syncytial sprouts vs. villous trophoblasts. LIN28B overexpression increased HTR8 cell proliferation, migration, and invasion, whereas LIN28B knockdown in JEG3 cells reduced cell proliferation. Moreover, LIN28B knockdown in JEG3 cells suppressed syncytin 1 (SYN-1), apelin receptor early endogenous ligand (ELABELA), and the chromosome 19 microRNA cluster, and increased mRNA expression of ITGβ4 and TNF-α. Incubation of BeWo and JEG3 cells under hypoxia significantly decreased expression of LIN28B and LIN28A, SYN-1, and ELABELA, whereas TNF-α is increased. These results provide the first evidence that LIN28B is the predominant paralog in human placenta and that decreased LIN28B may play a role in PE by reducing trophoblast invasion and syncytialization, and by promoting inflammation.-Canfield, J., Arlier, S., Mong, E. F., Lockhart, J., VanWye, J., Guzeloglu-Kayisli, O., Schatz, F., Magness, R. R., Lockwood, C. J., Tsibris, J. C. M., Kayisli, U. A., Totary-Jain, H. Decreased LIN28B in preeclampsia impairs human trophoblast differentiation and migration.

Project description:BackgroundThe immune microenvironment is a critical regulator of clear cell renal cell carcinoma (ccRCC) progression. However, the underlying mechanisms the regulatory role of immune-related long non-coding RNAs (irlncRNAs) in the ccRCC tumor microenvironment (TME) are still obscure. Herein, we investigated prognostics role of irlncRNAs for ccRCC.MethodsThe raw data of patients with ccRCC were downloaded from The Cancer Genome Atlas (TCGA) database, and immune-related genes were obtained from the ImmPort database. First, we investigated the correlation between the immune-related genes and irlncRNAs. Then, we identified the differentially expressed irlncRNA pairs (ILRPs) between normal and cancer tissue samples, and prognostic model was constructed with the differentially expressed ILRPs. We further explored whether the signature risk scores of ILRPs had a considerable impact on immune cell infiltration. Finally, we performed a drug sensitivity analysis based on risk score.ResultsThere were 13 upregulated and 40 downregulated irlncRNAs between the ccRCC and normal tissue samples. We further selected the irlncRNAs that significantly affect the prognosis of patients with ccRCC via univariate Cox, lasso regression, and multivariate regression analyses. Twelve ILRPs were used to construct a prognostic signature. The model showed the ILRPs model could be used to assess the prognosis of ccRCC patients. Study of the influence of risk score and clinical characteristics on the prognosis of patients with ccRCC showed risk score to be an independent factor affecting the outcome of ccRCC. We further performed the difference analysis of immune cell abundance between ccRCC and normal tissue samples. The results showed that patients with higher abundance of M0 macrophages, plasma cells, follicular helper T cells, and regulatory T cells (Tregs) had a poor outcome. Finally, we performed a drug sensitivity analysis based on risk score. The results showed that high-risk score patients are sensitive to orafenib, sunitinib, temsirolimus, cisplatin, and gemcitabine.ConclusionsOur study has developed a novel and reasonable ILPRs model for prognostic prediction, which does not require transcriptional levels to be detected.

Dataset Information

Long Non-Coding RNAs Serve as Diagnostic Biomarkers of Preeclampsia and Modulate Migration and Invasiveness of Trophoblast Cells.

Publications

Long Non-Coding RNAs Serve as Diagnostic Biomarkers of Preeclampsia and Modulate Migration and Invasiveness of Trophoblast Cells.

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