Xiao Dashu, Zhu Hongbin, Xiao Xin
Department of Pathology, Chaohu Hospital of Anhui Medical University, Chaohu, 238000, Anhui, China.
Department of Respiratory Medicine, Chaohu Hospital of Anhui Medical University, Chaohu, 238000, Anhui, China.
Appl Biochem Biotechnol. 2025 Jan;197(1):570-586. doi: 10.1007/s12010-024-05054-7. Epub 2024 Aug 29.
An upregulated histocompatibility minor 13 (HM13) has been studied in various tumors, yet the exact mechanism of HM13 in non-small cell lung cancer (NSCLC) is unclear. In view of same, the present study investigates crucial role and action mechanism of HM13 in human NSCLC. HM13 expression was higher in NSCLC tissue and cells through the Western blotting technique along with qRT-PCR. As per data from The Cancer Genome Atlas (TCGA), NSCLC patients having high HM13 expression show lower overall survival. 5-ethynyl-2-deoxyuridine (EdU), Cell Counting Kit-8 (CCK-8), and transwell tests were assessed for NSCLC cell growth, and invasion, and we found that silencing of HM13 inhibited the NSCLC cell proliferation, invasion. Additionally, to investigate the effects of HM13 on THP-1 macrophage polarization, a co-culture model of NSCLC and THP-1 macrophages were used. The CD206 + macrophages were examined using flow cytometry. As the markers of M2 macrophage, the mRNA levels of IL-10 and TGF-β of THP-1 cells were also detected by qRT-PCR. Knockdown of HM13 could inhibit the M2 polarization. Further experiments demonstrated that downregulated HM13 could inhibit the JAK2/STAT3 signaling pathway. RO8191 (activator of JAK/STAT3 pathway) influenced the invasion, proliferation, and expression of JAK2/STAT3 signaling pathway and Epithelial-mesenchymal transition (EMT) markers induced by HM13 silencing. HM13 knockdown also inhibited the tumor growth in vivo by xenograft nude mouse model. By inhibiting JAK2/STAT3 signaling pathway, HM13 knockdown inhibited the NSCLC cell proliferation, metastasis tumor growth, and tumor-associated macrophage M2 polarization. In NSCLC, HM13 could be a therapeutic target to treat the NSCLC.
组织相容性微小 13（HM13）上调已在多种肿瘤中得到研究，但 HM13 在非小细胞肺癌（NSCLC）中的确切机制尚不清楚。鉴于此，本研究探讨 HM13 在人 NSCLC 中的关键作用及作用机制。通过蛋白质免疫印迹技术和 qRT-PCR 检测发现，NSCLC 组织和细胞中 HM13 表达较高。根据癌症基因组图谱（TCGA）的数据，HM13 高表达的 NSCLC 患者总生存期较低。通过 5-乙炔基-2'-脱氧尿苷（EdU）、细胞计数试剂盒-8（CCK-8）和 Transwell 试验评估 NSCLC 细胞的生长和侵袭，发现沉默 HM13 可抑制 NSCLC 细胞增殖和侵袭。此外，为研究 HM13 对 THP-1 巨噬细胞极化的影响，使用了 NSCLC 与 THP-1 巨噬细胞的共培养模型。通过流式细胞术检测 CD206 +巨噬细胞。作为 M2 巨噬细胞的标志物，还通过 qRT-PCR 检测了 THP-1 细胞中白细胞介素-10（IL-10）和转化生长因子-β（TGF-β）的 mRNA 水平。敲低 HM13 可抑制 M2 极化。进一步实验表明，下调 HM13 可抑制 JAK2/STAT3 信号通路。RO8191（JAK/STAT3 通路激活剂）影响了由 HM13 沉默诱导的 JAK2/STAT3 信号通路的侵袭、增殖及上皮-间质转化（EMT）标志物的表达。敲低 HM13 还通过异种移植裸鼠模型抑制了体内肿瘤生长。通过抑制 JAK2/STAT3 信号通路，敲低 HM13 抑制了 NSCLC 细胞增殖、转移肿瘤生长及肿瘤相关巨噬细胞 M2 极化。在 NSCLC 中，HM13 可能是治疗 NSCLC 的一个治疗靶点。
