Dysregulated Expression of RPS4Y1 (Ribosomal Protein S4, Y-Linked 1) Impairs STAT3 (Signal Transducer and Activator of Transcription 3) Signaling to Suppress Trophoblast Cell Migration and Invasion in Preeclampsia

Chen, Xuehai; Tong, Chao; Li, Haiying; Peng, Wei; Li, Rong; Luo, Xin; Ge, Huisheng; Ran, Yuxin; Qin, Li; Liu, Yamin; Xiong, Xi; Bai, Yuxiang; Zhang, Hua; Baker, Philip N.; Liu, Xiru; Qi, Hongbo

doi:10.1161/hypertensionaha.117.10250

Cited by 34 publications

(22 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings suggest that STAT3 pathways play an important role in the pathogenesis of PE. Certain regulatory factors, such as RPS4Y1, HO-1, and HLA-G, have been reported to play a role in PE by affecting the expression and activation of STAT3 in trophoblast cells [20,34,35]. In the present study, we found that the STAT3 and p-STAT3 mRNA levels decreased following circPAPPA knockdown or miR-384 overexpression, and that this decrease could be reversed by co-transfection of miR-384 inhibitor and si-circPAPPA.…”

Section: Discussionsupporting

confidence: 57%

“…However, this process could also be partly reversed with the co-transfection of an miR-384 inhibitor and si-circPAPPA ( Figure 5D,E). The STAT3 pathway has been reported to be associated with PE, and studies have shown that STAT3 is a key regulator of trophoblast proliferation and invasion [19,20]. In addition, decreased expression and activation of STAT3 have been detected in PE patients [21].…”

Section: Examination Of the Role Of Regulation Of Circpappa And Mir-3mentioning

confidence: 99%

See 1 more Smart Citation

Down-regulated circPAPPA suppresses the proliferation and invasion of trophoblast cells via the miR-384/STAT3 pathway

et al. 2019

View full text Add to dashboard Cite

Preeclampsia (PE) is the main cause of maternal death in primipara, and commonly results in severe maternal and neonatal complications such as multiple organ dysfunction syndrome. However, the exact pathogenesis of this disease remains unclear. Circular RNAs (circRNAs) are noncoding RNAs that have been shown to be extensively involved in numerous physiological processes, but there is limited knowledge of their functions and mechanisms in PE. In the present study, we found the expression of a circRNA, hsa_circ_0088227 (circRNA of pregnancy-associated plasma protein A, circPAPPA), was down-regulated in both placenta and plasma samples from subjects with PE. Knockdown of circPAPPA led to decreased proliferation and invasion in HTR8-S/Vneo trophoblast cells. miR-384 was identified as a direct target of circPAPPA, and the gene encoding signal transducer and activator of transcription 3 (STAT3) was targeted by miR-384. We found that miR-384 was unregulated in PE, and overexpression of miR-384 could inhibit cell proliferation and invasion. In addition, we showed that the expression of STAT3 was decreased with knockdown of circPAPPA or the overexpression of miR-384 in trophoblast cells, but this decrease was partially reversed when co-transfection was performed with mimics of miR-384 inhibitor and si-circPAPPA. Together, these results suggest that down-regulation of circPAPPA facilitates the onset and development of PE by suppressing trophoblast cells, with involvement of the miR-384/STAT3 signaling pathway. Our study significantly increases the understanding of the occurrence and development of PE, and also provides a molecular target for the treatment of this disorder.

show abstract

Section: Discussionsupporting

confidence: 57%

Section: Examination Of the Role Of Regulation Of Circpappa And Mir-3mentioning

confidence: 99%

Down-regulated circPAPPA suppresses the proliferation and invasion of trophoblast cells via the miR-384/STAT3 pathway

et al. 2019

View full text Add to dashboard Cite

show abstract

“…This analysis highlighted only one novel gene, RPS4Y1, which passed the preselected criterion of the significance of the association. RPS4Y1 is a member of the S4E family of ribosomal proteins, which promotes PE by impairing STAT3 (Signal Transducer and Activator of Transcription 3) signaling and suppressing migration and invasion of trophoblast cells (28). Figure 3B shows that the product of RPS4Y1 may also promote the development of ASD through the activation of multiple membrane proteins, including CD86, CD80, and CD83.…”

Section: Discussionmentioning

confidence: 99%

Preeclampsia Drives Molecular Networks to Shift Toward Greater Vulnerability to the Development of Autism Spectrum Disorder

Xie

Wang

et al. 2020

Front. Neurol.

View full text Add to dashboard Cite

Preeclampsia (PE) confers a significant risk for subsequent diagnosis with autism spectrum disorder (ASD), with the mechanisms underlying this observation being largely unknown. To identify molecular networks affected by both PE and ASD, we conducted a large-scale literature data mining and a gene set enrichment analysis (GSEA), followed by an expression mega-analysis in 13 independently profiled ASD datasets. Sets of genes implicated in ASD and in PE significantly overlap (156 common genes; p = 3.14E −67), with many biological pathways shared (94 pathways; p < 1.00E −21). A set of PE-driven molecular triggers possibly contributing to worsening the risk of subsequent ASD was identified, possibly representing a regulatory shift toward greater vulnerability to the development of ASD. Mega-analysis of expression highlighted RPS4Y1, an inhibitor of STAT3 that is expressed in a sexually dimorphic manner, as a contributor to both PE and ASD, which should be evaluated as a possible contributor to male predominance in ASD. A set of PE-driven molecular triggers may shift the developing brain toward a greater risk of ASD. One of these triggers, chromosome Y encoded gene RPS4Y1, an inhibitor of STAT3 signaling, warrants evaluation as a possible contributor to male predominance in ASD.

show abstract

“…For instance, ribosomal protein S4 Y-linked 1 inhibits the migration and invasion of trophoblast cells in vitro and influences the growth of EVTs in villi placental explants by activating EMT-associated signaling pathways. 23 Our results showed that knockdown of RPL39 inhibited the proliferation, migration, and invasion of trophoblast cells in vitro. In addition, silencing RPL39 significantly suppressed the outgrowth capacity of EVTs in an ex vivo extravillous culture model.…”

Section: Discussionmentioning

confidence: 57%

Downregulated ribosomal protein L39 inhibits trophoblast cell migration and invasion by targeting E‐cadherin in the placenta of patients with preeclampsia

Jie

Sun

et al. 2021

The FASEB Journal

View full text Add to dashboard Cite

Early-onset preeclampsia (PE) is a pregnancy complication that can lead to severe adverse maternal and fetal outcomes. However, the mechanisms underlying the development of early-onset PE are not fully understood. Ribosomal protein L39 (RPL39) is a member of the S39E family of ribosomal proteins that plays an important role in stem cell self-renewal, cancer metastasis, and chemoresistance. In this study, we aimed to explore the potential function of RPL39 in placental trophoblast cells. We analyzed the expression of RPL39 in early-onset PE and normal placental tissues using real-time PCR, western blot analysis, and immunohistochemistry. The results showed that RPL39 was markedly downregulated in early-onset PE placental tissues. RPL39 knockdown inhibited trophoblast cell proliferation, migration, and invasion, as well as placental explant outgrowth. Flow cytometry analysis suggested that knockdown of RPL39 resulted in cell cycle arrest at the G0/G1 phase, but had no significant effect on cell apoptosis. We also found that RPL39 knockdown could alter cell morphology. We then measured the expression of the epithelial cell marker E-cadherin following knockdown of RPL39 in Bewo and HTR8/SVneo cells. RPL39 knockdown increased the expression of E-cadherin. Furthermore, E-cadherin expression was upregulated in placental explant outgrowth tissues transfected with RPL39 small interfering RNA. In conclusion, RPL39 plays an essential role in proliferation, invasion, and migration of trophoblast cells by targeting E-cadherin. Our findings provide novel insight into the mechanisms underlying the occurrence of early-onset PE.

show abstract

Dysregulated Expression of RPS4Y1 (Ribosomal Protein S4, Y-Linked 1) Impairs STAT3 (Signal Transducer and Activator of Transcription 3) Signaling to Suppress Trophoblast Cell Migration and Invasion in Preeclampsia

Cited by 34 publications

References 45 publications

Down-regulated circPAPPA suppresses the proliferation and invasion of trophoblast cells via the miR-384/STAT3 pathway

Down-regulated circPAPPA suppresses the proliferation and invasion of trophoblast cells via the miR-384/STAT3 pathway

Preeclampsia Drives Molecular Networks to Shift Toward Greater Vulnerability to the Development of Autism Spectrum Disorder

Downregulated ribosomal protein L39 inhibits trophoblast cell migration and invasion by targeting E‐cadherin in the placenta of patients with preeclampsia

Contact Info

Product

Resources

About