Zhang Zhen-Guo, Zhu Hong-Mei, Hua Huai-Kang
Plastic and Reconstructive Surgery, Lishui People' s Hospital, Lishui, Zhejiang, China.
General practice, Xin Bi Community Health Center, Lishui, Zhejiang, China.
Skin Res Technol. 2024 Mar;30(3):e13618. doi: 10.1111/srt.13618.
This study aimed to investigate the role of Interleukin-11 receptor alpha (IL11RA) in skin cutaneous melanoma (SKCM) metastasis to the liver.
Human SKCM cell lines (A375, A375-MA2, SK-MEL-28, RPMI-7951) and primary dermal fibroblasts (HDFa) were utilized to assess IL11RA expression. IL11RA siRNA was transfected into RPMI-7951 and A375-MA2 cells for Wound healing and Transwell invasion assays. Il11ra knockout (KO) mice and wild-type (WT) mice were injected with B16-F10 cells into the spleen to evaluate hepatic melanoma metastasis. Correlation between IL11RA and MMP family genes was explored using online databases, including LinkedOmics, TIMER (Tumor Immune Estimation Resource), and GEPIA (Gene Expression Profiling Interactive Analysis). RT-qPCR and Western blotting were performed for expression analysis of Mmp2 and Mmp9 in liver tissues of mice. The impact of IL11RA on the STAT3 pathway was investigated in vitro and in vivo.
Elevated expression of IL11RA was observed in SKCM cell lines compared to normal cells. IL11RA downregulation significantly inhibited migratory and invasive capabilities of A375-MA2 and RPMI-7951 in vitro. Il11ra gene knockout in mice demonstrated a substantial reduction in hepatic melanoma metastasis. Correlation analyses revealed associations between IL11RA and MMP2/MMP8. Il11ra gene knockout significantly decreased Mmp2 expression while increasing Mmp8 in liver tissues. IL11RA correlated positively with STAT3, and its inhibition led to a suppressed STAT3 pathway in SKCM cells and mouse liver tissue.
IL11RA plays a crucial role in SKCM metastasis, affecting migratory and invasive abilities. Targeting IL11RA may offer a promising avenue for therapeutic interventions in cutaneous melanoma progression.
本研究旨在探讨白细胞介素-11受体α（IL11RA）在皮肤黑色素瘤（SKCM）肝转移中的作用。
利用人SKCM细胞系（A375、A375-MA2、SK-MEL-28、RPMI-7951）和原代表皮成纤维细胞（HDFa）评估IL11RA的表达。将IL11RA siRNA转染到RPMI-7951和A375-MA2细胞中进行伤口愈合和Transwell侵袭试验。将Il11ra基因敲除（KO）小鼠和野生型（WT）小鼠经脾脏注射B16-F10细胞，以评估肝黑色素瘤转移情况。利用在线数据库（包括LinkedOmics、TIMER（肿瘤免疫评估资源）和GEPIA（基因表达谱交互分析））探索IL11RA与MMP家族基因之间的相关性。对小鼠肝脏组织中的Mmp2和Mmp9进行RT-qPCR和蛋白质印迹分析以检测其表达。在体外和体内研究IL11RA对STAT3信号通路的影响。
与正常细胞相比，SKCM细胞系中IL11RA的表达升高。IL11RA下调显著抑制了A375-MA2和RPMI-7951在体外的迁移和侵袭能力。小鼠Il11ra基因敲除显示肝黑色素瘤转移显著减少。相关性分析揭示了IL11RA与MMP2/MMP8之间的关联。Il11ra基因敲除显著降低了肝脏组织中Mmp2的表达，同时增加了Mmp8的表达。IL11RA与STAT3呈正相关，其抑制导致SKCM细胞和小鼠肝脏组织中的STAT3信号通路受到抑制。
IL11RA在SKCM转移中起关键作用，影响迁移和侵袭能力。靶向IL11RA可能为皮肤黑色素瘤进展的治疗干预提供一个有前景的途径。
