目的：探讨长链非编码RNA小泛素样修饰蛋白1假基因3（lncRNA SUMO1P3）促进肝细胞癌（HCC）HepG2细胞对索拉菲尼（SR）耐药的分子机制。方法：体外培养HCC细胞HepG2，采用持续接触浓度递增诱导法建立SR耐药细胞HepG2/SR，以HepG2细胞作为对照，qPCR 法检测 HepG2/SR 细胞中 SUMO1P3 的表达。利用脂质体转染技术，在 HepG2/SR细胞中分别转染si-SUMO1P3和si-NC；在HepG2细胞中分别转染pc-SUMO1P3和pc-DNA，后经5 μmol/L的SR处理24 h，qPCR法检测转染细胞中SUMO1P3表达水平，CCK-8法、Transwell实验和FCM分别检测转染细胞的增殖、迁移和侵袭能力和凋亡水平，WB法检测细胞中cyclin D1、Bcl2、BAX、MMP-2和MMP-9的表达。结果：成功构建SR耐药细胞HepG2/SR，HepG2/SR细胞中SUMO1P3表达水平显著高于 HepG2 细胞（P<0.01）。在 HepG2/SR 细胞敲减 SUMO1P3 后 ，与 si-NC 组比较 ，si-SUMO1P3 组细胞中SUMO1P3的表达与细胞增殖、迁移、侵袭能力及cyclin D1、Bcl2、MMP-2和MMP-9表达均显著降低，细胞凋亡率和BAX的表达均显著升高（P<0.05或P<0.01）。HepG2细胞过表达SUMO1P3后，与pc-DNA组比较，pc-SUMO1P3组细胞的增殖、迁移、侵袭能力及cyclin D1、Bcl2、MMP-2和MMP-9蛋白表达均显著升高，细胞凋亡率和BAX的表达均降低（P<0.05 或 P<0.01）；与pc-DNA+SR组比较，pc-SUMO1P3+SR组HepG2细胞的增殖、迁移、侵袭能力及cyclin D1、Bcl2、MMP-2和MMP-9蛋白表达均显著升高，细胞凋亡率和BAX的表达均显著降低（P<0.05或P<0.01）。结论：lncRNA SUMO1P3可通过调控HCC细胞的周期、凋亡等多种信号通路分子诱导细胞对SR的耐药，从而影响HepG2细胞的增殖、迁移和侵袭，并抑制细胞凋亡与诱导细胞对SR的耐药。

Objective:Toinvestigatethemolecular mechanisms of sorafenib (SR) resistance induced by long non-coding RNA small ubiquitinlike modifier 1 pseudogene 3 (lncRNA SUMO1P3) in hepatocellular carcinoma (HCC). Methods: HCC cells HepG2 were cultured in vitro and acted as the control group. The expression of SUMO1P3 was detected by qPCR in HepG2/SR cells, which was induced by continuously increasing the contact concentration. si-SUMO1P3 and si-NC were transfected into HepG2/SR cells by Lipofectamine. pc-SUMO1P3 and pc-DNA were transfected into HepG2 cells respectively, and then treated with 5 μmol/L SR for 24 hours. qPCR was used to detect the expression levels of SUMO1P3 in the transfected cells. The proliferation, migration, invasion and apoptosis of transfected cells were detected by CCK-8, Transwell assay, and FCM, respectively. Western blotting assay was conducted to detect the expression of cyclin D1,Bcl2,BAX,MMP-2, and MMP-9 in the different cell groups. Results: Sorafenib-resistant HepG2/SR cells were successfully constructed.The expression level of SUMO1P3 in the HepG2/SR cells was significantly higher than that in the HepG2 cells(P<0.01).After SUMO1P3 was knocked outintheHepG2/SRcells, comparedwithinthe si-NC group,inthe si-SUMO1P3 group the expression of SUMO1P3, the proliferation, migration and invasion of cells and the protein levels of cyclin D1, Bcl2, MMP-2 and MMP-9 were all significantly lower while the percentage of apoptotic cells and the expression of BAX were significantly higher (P<0.05 or P<0.01). After SUMO1P3 was over-expressed in the HepG2 cells, compared with in the pc-DNA group, the proliferation, migration and invasion of cells in the pc-SUMO1P3 group and the protein levels of cyclin D1, Bcl2, MMP-2 and MMP-9 were all significantly higher while the percentage of apoptotic cells and the expression of BAX were significantly lower (P<0.05 or P<0.01). Similarly, compared with in the pc-DNA+SR group, the proliferation, migration and invasion of HepG2 cells in the pc-SUMO1P3+SR group and the protein levels of cyclin D1, Bcl2, MMP-2 and MMP-9 were all significantly higher while the percentage of apoptotic cells and the expression of BAX were significantly lower (P<0.05 or P<0.01). Conclusion: lncRNA SUMO1P3 can induce the resistance of HepG2 cells to sorafenib by promoting the proliferation, migration and invasion and inhibiting the apoptosis of HepG2 cells.

河南省医学科技攻关计划联合共建项目（No.LHGJ20210529）