长链非编码 RNA TARID 在滋养细胞中调节 CXCL3/ERK/MAPK 通路，与子痫前期有关。
The long noncoding RNA TARID regulates the CXCL3/ERK/MAPK pathway in trophoblasts and is associated with preeclampsia.
机构信息
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) of Ministry of Education, Chengdu, Sichuan, China.
Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
出版信息
Reprod Biol Endocrinol. 2022 Nov 19;20(1):159. doi: 10.1186/s12958-022-01036-8.
BACKGROUND
The widely accepted explanation of preeclampsia (PE) pathogenesis is insufficient trophoblast invasion and impaired uterine spiral artery remodeling. However, the underlying molecular mechanism remains unclear.
METHODS
We performed transcriptome sequencing on placentas of normal and PE patients and identified 976 differentially expressed long noncoding RNAs (lncRNAs). TCF21 antisense RNA inducing demethylation (TARID) was one of the most significantly differentially expressed lncRNAs and was negatively correlated with the systolic and diastolic blood pressure in PE patients. Furthermore, we verified the effect of TARID on the biological behavior of trophoblasts and performed UID mRNA-seq to identify the effectors downstream of TARID. Then, co-transfection experiments were used to better illustrate the interaction between TARID and its downstream effector.
RESULTS
We concluded that the downregulation of TARID expression may inhibit trophoblast infiltration and spiral artery remodeling through inhibition of cell migration, invasion, and tube formation mediated through the CXCL3/ERK/MAPK pathway.
CONCLUSIONS
Overall, these findings suggested that TARID may be a therapeutic target for PE through the CXCL3/ERK/MAPK pathway.
背景
子痫前期（PE）发病机制的广泛接受的解释是滋养细胞侵袭不足和子宫螺旋动脉重塑受损。然而，其潜在的分子机制仍不清楚。
方法
我们对正常和 PE 患者的胎盘进行了转录组测序，鉴定出 976 个差异表达的长非编码 RNA（lncRNA）。TCF21 反义 RNA 诱导去甲基化（TARID）是差异表达最显著的 lncRNA 之一，与 PE 患者的收缩压和舒张压呈负相关。此外，我们验证了 TARID 对滋养细胞生物学行为的影响，并进行了 UID mRNA-seq 以鉴定 TARID 的下游效应物。然后，共转染实验用于更好地说明 TARID 与其下游效应物之间的相互作用。
结果
我们得出结论，TARID 表达的下调可能通过抑制 CXCL3/ERK/MAPK 通路介导的细胞迁移、侵袭和管形成来抑制滋养细胞浸润和螺旋动脉重塑。
结论
总的来说，这些发现表明 TARID 可能通过 CXCL3/ERK/MAPK 通路成为治疗 PE 的靶点。
Zotero 插件