miR-655通过靶向PTTG1调节胎盘滋养细胞的侵袭能力  

miR-655 regulates the invasive capacity of placental trophoblast cells by targeting PTTG1

作　　者：祖丽菲娅·阿布力克木 伊丽努尔·阿布力孜 迪福扎·热合木丁 黄莺[1] ZULIFEIYA Abulikemu;YILINUER Abulizi;DIFUZHA Rehemuding;HUANG Ying(Department of Obstetrics and Gynecology,People’s Hospital of Xinjiang Uygur Autonomous Region,Urumqi,Xinjiang 830001,China;Department of Obstetrics and Gynecology,Clinical Medicine,Xinjiang Medical University,Urumqi,Xinjiang 830054,China)

机构地区：[1]新疆维吾尔自治区人民医院妇产科,新疆乌鲁木齐830001 [2]新疆医科大学临床医学部产科,新疆乌鲁木齐830054

出　　处：《中国优生与遗传杂志》2024年第12期2461-2467,共7页Chinese Journal of Birth Health & Heredity

基　　金：新疆维吾尔自治区自然科学基金面上项目(2023D01C88)。

摘　　要：目的探讨微小RNA(miR)-655通过靶向垂体瘤转化基因1(PTTG1)并调节PI3K/Akt/MMP-9信号通路对胎盘滋养细胞侵袭能力的影响。方法选取2021年6月至2023年6月新疆维吾尔自治区人民医院妇产科住院患者纳入研究对象,根据胎盘超声检查结果分为胎盘植入异常(PA)患者30例和正常对照组(PC)30例。采用qRT-PCR检测两组胎盘组织中miR-655和PTTG1的表达,同时以胎盘滋养细胞(HTR8/SVneo)为模型评估其对细胞侵袭和迁移的影响。利用Transwell侵袭实验和细胞划痕实验检测干扰或过表达miR-655对HTR8/SVneo细胞侵袭和迁移的影响。通过Western blot检测磷酸化(p-PI3K)和磷脂酰肌醇3激酶(PI3K)、磷酸化(p-Akt)和蛋白激酶B(Akt)和基质金属蛋白酶9(MMP-9)的蛋白表达水平,验证信号通路的激活情况。结果与PC组相比,PA组胎盘组织中miR-655的表达显著下调(P<0.05),而PTTG1的表达显著上调(P<0.05)。干扰实验显示,抑制miR-655显著增强滋养细胞的侵袭和迁移能力(P<0.05),而过表达miR-655则显著抑制其侵袭和迁移能力(P<0.05)。此外,Western blotting结果显示,miR-655过表达后,p-PI3K、p-Akt和MMP-9的蛋白表达水平显著降低(P<0.05),表明miR-655通过下调PTTG1抑制了PI3K/Akt/MMP-9信号通路的活化。结论miR-655在PA胎盘组织中低表达,并通过靶向PTTG1调控PI3K/Akt/MMP-9信号通路,抑制胎盘滋养细胞的侵袭和迁移能力。该研究揭示了miR-655和PTTG1在PA中的重要作用,并为临床治疗提供了新的潜在靶点,有望成为PA诊断和治疗的新方向。Objective To investigate the effect of miR-655 on the invasive potential of placental trophoblast cells by targeting PTTG1 and modulating the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/matrix metalloproteinase 9(MMP-9)signaling pathway.Methods Patients admitted to the Department of Obstetrics and Gynecology at the People’s Hospital of Xinjiang Uygur Autonomous Region from June 2021 to June 2023 were selected as the study subjects.Based on placental ultrasound examination results,they were divided into an abnormal placental implantation group(PA)with 30 cases and a normal control group(PC)with 30 cases.The expression levels of miR-655 and PTTG1 in placental tissue of both groups were detected using qRT-PCR.The impact of miR-655 on cell invasion and migration was assessed in the placental trophoblast cell line HTR8/SVneo.Transwell invasion and scratch assays were performed to evaluate the impact of miR-655 knockdown or overexpression on the invasion and migration of HTR8/SVneo cells.Western blotting was used to measure the protein expression levels of PI3K,p-PI3K,Akt,p-Akt,and MMP-9,thereby verifying the activation of the signaling pathway.Results Compared to the PC group,miR-655 expression was significantly downregulated(P<0.05),whereas PTTG1 expression was significantly upregulated(P<0.05)in PA placental tissues.Knockdown experiments showed that inhibition of miR-655 significantly enhanced the invasion and migration capabilities of trophoblast cells(P<0.05),whereas miR-655 overexpression significantly reduced these capabilities(P<0.05).Additionally,Western blot results indicated that the protein levels of p-PI3K,p-Akt,and MMP-9 were significantly decreased following miR-655 overexpression(P<0.05),suggesting that miR-655 inhibits the activation of the PI3K/Akt/MMP-9 signaling pathway by downregulating PTTG1.Conclusion miR-655 is under expressed in PA placental tissues and inhibits the invasion and migration capabilities of placental trophoblast cells by targeting PTTG1 and modulating the PI3K/Akt/MMP-

关 键 词：胎盘植入 微RNA-655(miR-655) 垂体瘤转化基因1(PTTG1) 侵袭 

分 类 号：R714.2[医药卫生—妇产科学]