SOCS2 过表达抑制宫颈癌 IL-6/JAK2/STAT3 通路 EMT 和 M2 型巨噬细胞极化
Overexpression of SOCS2 Inhibits EMT and M2 Macrophage Polarization in Cervical Cancer IL-6/JAK2/STAT3 Pathway.
机构信息
Department of Gynecologic Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People's Republic of China.
Department of Gynecologic, Guangxi Medical University Affiliated National Hospital, Nanning, Guangxi, 530021, People's Republic of China.
出版信息
Comb Chem High Throughput Screen. 2024;27(7):984-995. doi: 10.2174/1386207326666230818092532.
OBJECTIVE
SOCS2 is a member of the suppressor of cytokine signaling (SOCS) protein family associated with the occurrence and development of multiple cancers. This study revealed the expression and molecular mechanisms of SOCS2 in cervical cancer.
METHODS
In this study, RT-qPCR, Western Blot, and immunohistochemistry were used to detect the expression level of SOCS2 in cervical cancer tissues and tumor cells. We overexpressed SOCS2 in SiHa cells lentivirus. experiments were used to investigate the changes in cervical cancer cell proliferation, migration, and invasion ability before and after SOCS2 overexpression. Western Blot was used to detect the expression of IL-6/JAK2/STAT3 pathway and EMTrelated proteins. M0 macrophages were co-cultured with the tumor-conditioned medium. The effect of SOCS2 on macrophage polarization was examined by RT-qPCR.
RESULTS
SOCS2 expression level was significantly downregulated in cervical cancer tissues. SOCS2 was negatively correlated with CD163+M2 macrophages. Overexpression of SOCS2 inhibited the proliferation, migration, and invasion of cervical cancer cells. The expressions of Twist- 2, N-cadherin, and Vimentin were decreased, while the expression of E-cadherin was increased. Moreover, the expression of IL-6, p-JAK2, and p-STAT3 were decreased. After the addition of RhIL-6, the expression of E-cadherin protein in the LV-SOCS2 group was reversed. CM in the LV-SOCS2 group inhibited the polarization of M2 macrophages.
CONCLUSION
SOCS2 acts as a novel biological target and suppressor of cervical cancer through IL- 6/JAK2/STAT3 pathway.
目的
SOCS2 是细胞因子信号转导抑制因子（SOCS）蛋白家族的一员，与多种癌症的发生和发展有关。本研究揭示了 SOCS2 在宫颈癌中的表达及其分子机制。
方法
本研究采用 RT-qPCR、Western blot 和免疫组织化学方法检测 SOCS2 在宫颈癌组织和肿瘤细胞中的表达水平。我们通过慢病毒过表达 SiHa 细胞中的 SOCS2。实验用于研究 SOCS2 过表达前后宫颈癌细胞增殖、迁移和侵袭能力的变化。Western blot 用于检测 IL-6/JAK2/STAT3 通路和 EMT 相关蛋白的表达。M0 巨噬细胞与肿瘤条件培养基共培养。通过 RT-qPCR 检测 SOCS2 对巨噬细胞极化的影响。
结果
SOCS2 在宫颈癌组织中的表达水平明显下调。SOCS2 与 CD163+M2 巨噬细胞呈负相关。SOCS2 的过表达抑制了宫颈癌细胞的增殖、迁移和侵袭。Twist-2、N-钙粘蛋白和波形蛋白的表达减少，而 E-钙粘蛋白的表达增加。此外，IL-6、p-JAK2 和 p-STAT3 的表达减少。加入 RhIL-6 后，LV-SOCS2 组 E-钙粘蛋白蛋白的表达得到逆转。LV-SOCS2 组 CM 抑制 M2 巨噬细胞的极化。
结论
SOCS2 通过 IL-6/JAK2/STAT3 通路作为宫颈癌的新型生物靶标和抑制剂发挥作用。
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