Differentially expressed circular RNAs and the competing endogenous RNA network associated with preeclampsia

Ma, Bo; Zhao, Huanqiang; Gong, Lili; Xiao, Xirong; Zhou, Qionggui; Lu, Huiqing; Cui, Yutong; Xu, Huangfang; Wu, Suwen; Tang, Yao; Ye, Yunzhen; Gu, Weirong; Li, Xiaotian

doi:10.1016/j.placenta.2020.10.010

Cited by 20 publications

(14 citation statements)

References 36 publications

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“…[19,20] Accumulating studies have highlighted the effective regulation of circRNA-miRNA-mRNA network in PE development. [21,22] Therefore, we studied the circTNC/miR-525-5p/ABL1 axis in PE and the key findings demonstrated that circTNC binds with miR-525-5p and upregulated ABL1 expression, thereby repressing trophoblast migration and invasion, which aggravates PE development progression.…”

Section: Discussionmentioning

confidence: 99%

Hsa_circ_0088196 suppresses trophoblast migration and invasion by the miR‐525‐5p/ABL1 axis and the PI3K/AKT signaling pathway

Shi

2022

J Biochem & Molecular Tox

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Our study aimed to explore the role of circ_0088196 (circular TNC [circTNC]) in trophoblast invasion and migration in preeclampsia (PE) both in vitro and in vivo. CircTNC, miR‐525‐5p, and ABL1 expression in trophoblast HTR8/SVneo cells were evaluated by quantitative real‐time polymerase chain reaction (qRT‐PCR). Cell viability, migration, and invasion were detected by Cell Counting Kit‐8 (CCK‐8), wound healing, and Transwell assays. The binding between circTNC (or ABL1) and miR‐525‐5p was validated by RNA pulldown and luciferase reporter assays. The mouse model of PE was injected with sh‐circTNC and the effects of circTNC knockdown on the mean artery pressure, urine protein concentration, and fetal survival number of pregnant mice were examined. The expression of MMP‐2, MMP‐9, and PI3K/AKT pathway molecules in placental tissues was assessed by immunohistochemistry, qRT‐PCR, and western blot analysis. CircTNC overexpression inhibited cell invasion and migration, but did not influence cell proliferation. CircTNC bound with miR‐525‐5p, whose knockdown repressed cell invasion and migration, while it exerted no effect on cell proliferation. ABL1, a target of miR‐525‐5p, attenuated cell migration and invasion, without influence on cell viability. Importantly, either miR‐525‐5p overexpression or ABL1 depletion antagonized the repression of upregulated circTNC on trophoblast cell migration and invasion, MMP‐2 and MMP‐9 expression, and the PI3K/AKT pathway. CircTNC knockdown alleviated PE symptoms in pregnant mice. CircTNC knockdown promoted the trophoblast invasiveness in mice placenta by upregulating MMP‐2/9 expression and suppressing the PI3K/AKT pathway. Circ_0088196 represses trophoblast invasion and migration both in vitro and in vivo via regulating the miR‐525‐5p/ABL1 axis and activating the PI3K/AKT pathway.

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Section: Discussionmentioning

confidence: 99%

Hsa_circ_0088196 suppresses trophoblast migration and invasion by the miR‐525‐5p/ABL1 axis and the PI3K/AKT signaling pathway

Shi

2022

J Biochem & Molecular Tox

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“…Our findings first disclosed that circ-OPHN1 overexpression suppressed cell viability, migration and invasion, but facilitated cell apoptosis in trophoblast cells. Numerous reports have suggested that circRNAs participated in the regulation of PE progression through the ceRNA mechanism (Hu et al, 2018;Ma et al, 2020). For example, circ_0111277 decelerated the invasion and migration of trophoblast cells in PE through miR-494/HTRA1 axis (Ou et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…As another cluster of small noncoding RNAs, microRNAs (miRNAs) with a length of approximately 22 nucleotides, were also suggested to exert crucial roles in the pathological process of PE (Lv et al, 2019). Extensive results have identified that circRNAs could exert its function in PE by serving as miRNA sponges to adjust miRNA interactions with their downstream targets (Ma et al, 2021; Yamamura et al, 2018). For instance, circ_0063517 acted as a sponge for miR‐31‐5p to regulate ETBR expression, thereby regulating the angiogenesis of vascular endothelial cells in PE (W. Li, Yu, et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Circ‐OPHN1 suppresses the proliferation, migration, and invasion of trophoblast cells through mediating miR‐558/THBS2 axis

Chen

Song

2022

Drug Development Research

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Preeclampsia (PE) is one of the most serious diseases during pregnancy. Circular RNAs (circRNAs) are strongly related to the occurrence of preeclampsia. Herein, we aimed to explore the potential role and mechanism of circRNA oligophrenin 1 (circ-OPHN1; hsa_circ_0007445) in PE. Quantitative real-time polymerase chain reaction (qPCR) and western blot were utilized to detect gene expression levels. The biological behaviors of trophoblast cells were determined by 3-(4,5-dimethyl-2-thiazolyl) −2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry, transwell, and wound healing methods. The binding relationship between microRNA-558 (miR-558) and circ-OPHN1 or thrombospondin 2 (THBS2) was validated via dual-luciferase reporter assay. Circ-OPHN1 and THBS2 levels were enhanced, while miR-558 level was declined in PE placental tissues. Circ-OPHN1 or THBS2 overexpression hindered the proliferation, migration, and invasion of trophoblast cells. In addition, circ-OPHN1 sequestered miR-558 to regulate THBS2 expression, thereby repressing the growth and mobility of trophoblast cells. Circ-OPHN1 inhibited trophoblast cell proliferation, migration, and invasion through mediating miR-558/ THBS2 axis, providing a novel pathway for PE pathogenesis.

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“…Circular RNAs (circRNAs) are long non-coding RNAs usually formed by alternative splicing of pre-mRNA, where the 5′ upstream splice acceptor is joined to the 3′ downstream splice donor in a process named “backsplicing” [ 48 ]. Growing evidence reveals that circRNAs behave as a competing endogenous RNA (ceRNA) by acting as a miRNA “sponge”, thus reducing miRNA regulatory effect on the expression of the downstream genes [ 49 ]. CircRNAs have a significant role in regulating gene expression in gametogenesis, embryogenesis, and cell differentiation [ 50 ].…”

Section: Ncrnas As Potential Biomarkersmentioning

confidence: 99%

“…In detail, specific circRNAs were found to be downregulated in plasma of pregnant women with GDM [ 52 ]. Furthermore, a differential expression profile of circRNAs [ 53 , 54 ], as well as a modified circRNA–miRNA–mRNA network [ 49 ], were also associated with PE.…”

Section: Ncrnas As Potential Biomarkersmentioning

confidence: 99%

Significance of Sex Differences in ncRNAs Expression and Function in Pregnancy and Related Complications

et al. 2021

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In the era of personalized medicine, fetal sex-specific research is of utmost importance for comprehending the mechanisms governing pregnancy and pregnancy-related complications. In recent times, noncoding RNAs (ncRNAs) have gained increasing attention as critical players in gene regulation and disease pathogenesis, and as candidate biomarkers in human diseases as well. Different types of ncRNAs, including microRNAs (miRNAs), piwi-interacting RNAs (piRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), participate in every step of pregnancy progression, although studies taking into consideration fetal sex as a central variable are still limited. To date, most of the available data have been obtained investigating sex-specific placental miRNA expression. Several studies revealed that miRNAs regulate the (patho)-physiological processes in a sexually dimorphic manner, ensuring normal fetal development, successful pregnancy, and susceptibility to diseases. Moreover, the observation that ncRNA profiles differ according to cells, tissues, and developmental stages of pregnancy, along with the complex interactions among different types of ncRNAs in regulating gene expression, strongly indicates that more studies are needed to understand the role of sex-specific ncRNA in pregnancy and associated disorders.

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Differentially expressed circular RNAs and the competing endogenous RNA network associated with preeclampsia

Cited by 20 publications

References 36 publications

Hsa_circ_0088196 suppresses trophoblast migration and invasion by the miR‐525‐5p/ABL1 axis and the PI3K/AKT signaling pathway

Hsa_circ_0088196 suppresses trophoblast migration and invasion by the miR‐525‐5p/ABL1 axis and the PI3K/AKT signaling pathway

Circ‐OPHN1 suppresses the proliferation, migration, and invasion of trophoblast cells through mediating miR‐558/THBS2 axis

Significance of Sex Differences in ncRNAs Expression and Function in Pregnancy and Related Complications

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