摘 要：为探讨长链非编码核糖核酸（LncRNA）MAGI2-AS3调节miR-143-3p/PTP4A1轴对宫颈癌（CC）细胞的影响，通过RT-qPCR检测54例CC患者术中切除的CC组织及癌旁组织中MAGI2-AS3、miR-143-3p、PTP4A1的表达。将HeLa细胞随机分为对照组、sh-NC组、sh-MAGI2-AS3组、sh-MAGI2-AS3+anti-NC组、sh-MAGI2-AS3+anti-miR-143-3p组，测定各组细胞中MAGI2-AS3、miR-143-3p、PTP4A1的表达；检测细胞的增殖、迁移、侵袭情况及PTP4A1、基质金属蛋白酶-2（MMP-2）、MMP-9、增殖细胞核抗原（PCNA）蛋白的表达。利用动物试验验证敲除MAGI2-AS3对CC肿瘤生长及PTP4A1表达的影响。结果显示：CC组织MAGI2-AS3、PTP4A1 mRNA的表达量分别为1.97±0.35、1.73±0.34，高于癌旁组织（1.02±0.33、0.98±0.31），miR-143-3p表达量为0.48±0.14，低于癌旁组织（1.01±0.16）（P<0.05）。相较于sh-NC组和对照组，sh-MAGI2-AS3组HeLa细胞中的A490 nm值、EdU阳性细胞率、划痕愈合率、侵袭数以及MAGI2-AS3、PTP4A1 mRNA的表达量和PCNA、PTP4A1、MMP-2、MMP-9蛋白的表达水平均降低，miR-143-3p mRNA的表达量升高（P<0.05）。相较于sh-MAGI2-AS3组、sh-MAGI2-AS3+anti-NC组，sh-MAGI2-AS3+anti-miR-143-3p组miR-143-3p mRNA的表达量降低，A490 nm值、EdU阳性细胞率、划痕愈合率、侵袭数以及PTP4A1 mRNA的表达量和PCNA、PTP4A1、MMP-2、MMP-9蛋白的表达水平升高（P<0.05）。相较于sh-NC组，sh-MAGI2-AS3组移植瘤的质量、体积、Ki-67阳性率、PTP4A1阳性率均降低（P<0.05）。综上所述，MAGI2-AS3靶向负调控miR-143-3p，miR-143-3p靶向负调控PTP4A1。敲除MAGI2-AS3可能抑制CC细胞的侵袭、迁移和增殖，可能是通过调节miR-143-3p/PTP4A1轴实现的。本研究可能为CC的靶向治疗研究提供新的靶点。
关键词：LncRNA MAGI2-AS3；miR-143-3p/PTP4A1轴；宫颈癌；迁移；侵袭
中图分类号：R737.33                        文献标志码：A                    DOI：10.3969/j.issn.1007-7146.2025.04.009

Abstract: To explore the effects of long non-coding ribonucleic acid (LncRNA) MAGI2-AS3 in regulating the miR-143-3p/PTP4A1 axis on cervical cancer (CC) cells, the expressions of MAGI2-AS3, miR-143-3p and PTP4A1 in the resected CC tissues and adjacent tissues of 54 patients with CC during the operation were detected by RT-qPCR. HeLa cells were randomly divided into control group, sh-NC group, sh-MAGI2-AS3 group, sh-MAGI2-AS3+anti-NC group and sh-MAGI2-AS3+anti-miR-143-3p group. The expression of MAGI2-AS3, miR-143-3p and PTP4A1 in each group was measured. Cell proliferation, migration, and invasion, expressions of PTP4A1, matrix metalloproteinase-2 (MMP-2), MMP-9 and proliferating cell nuclear antigen (PCNA) were detected. The effects of MAGI2-AS3 knockout on CC tumor growth and PTP4A1 expression were verified by animal experiments. The results showed: the expression levels of MAGI2-AS3 and PTP4A1 mRNA in CC tissues was 1.97±0.35, 1.73±0.34, higher than (1.02±0.33, 0.98±0.31) in adjacent tissues, and the expression levels of miR-143-3p was 0.48±0.14, lower than (1.01±0.16) in adjacent tissues (P<0.05). Compared with the sh-NC group and the control group, the A490 nm value, EdU positive cell rate, scratch healing rate, invasion number, mRNA expression levels of MAGI2-AS3 and PTP4A1, and protein expression levels of PCNA, PTP4A1, MMP-2 and MMP-9 in HeLa cells of the sh-MAGI2-AS3 group were all decreased; the mRNA expression level of miR-143-3p increased (P<0.05). Compared with the sh-MAGI2-AS3 group and the sh-MAGI2-AS3+anti-NC group, the mRNA expression level of miR-143-3p in the sh-MAGI2-AS3+anti-miR-143-3p group decreased, the A490 nm value, the rate of EdU positive cells, the scratch healing rate, the number of invasions, as well as the mRNA expression levels of PTP4A1 and the protein expression levels of PCNA, PTP4A1, MMP-2 and MMP-9 increased (P<0.05). Compared with the sh-NC group, the mass, volume, positive rate of Ki-67 and positive rate of PTP4A1 of the transplanted tumors in the sh-MAGI2-AS3 group were all decreased (P<0.05). To sum up, MAGI2-AS3 targeted negative regulation of miR-143-3p; miR-143-3p negatively regulates PTP4A1. Knockout of MAGI2-AS3 may inhibit the proliferation, migration and invasion of CC cells, which may be achieved by regulating the miR-143-3p/PTP4A1 axis.
Key word: LncRNA MAGI2-AS3; miR-143-3p/PTP4A1 axis; cervical cancer; migration; invasion
（Acta Laser Biology Sinica, 2025, 34(4): 365-373）