中国肿瘤生物治疗杂志2026，Vol.33Issue(4)：379-388,10.DOI:10.3872/j.issn.1007-385x.2026.04.004
HOXD11通过转录调控Ki-67活性促进喉鳞状细胞癌细胞的恶性生物学行为
HOXD11 promotes the malignant biological behaviors of laryngeal squamous cell carcinoma through transcriptional regulation of Ki-67 activity
摘要
Abstract
Objective:To investigate the transcriptional regulation of HOXD11(homeobox D11)on Ki-67,its effects on the malignant biological behavior of laryngeal squamous cell carcinoma(LSCC)cells and the underlying mechanisms.Methods:High-throughput sequencing data from GEO and UALCAN databases were used to analyzed the differential expression of HOXD11 in LSCC.Tumor and adjacent tissue specimens from 60 patients with LSCC surgically resected at the 980 Hospital of the Joint Logistics Support Force between January 2022 and January 2025,along with human LSCC cell lines AMC-HN-8,TU-177,TU-686,and human normal laryngeal epithelial cells(HNLEC)were collected.Cell lines with stable HOXD11 knockdown or overexpression were established,and the cells were divided into the control group,the HOXD11 knockdown group,and the HOXD11 overexpression group.The mRNA expression levels of HOXD11 and Ki-67 genes in LSCC tissues and cells were detected by RT-qPCR.The protein expression and distribution of HOXD11 and Ki-67 in LSCC tissues were analyzed by immunohistochemistry(IHC).Western blot(WB)further verified protein differential expression.MTS,clonogenic assay and Transwell assay were used to detect the effects of HOXD11 knockdown or overexpression on the proliferation,migration and invasion of LSCC cells.Dual luciferase reporter gene experiment and ChIP experiment were used to confirm the regulatory effect of HOXD11 on Ki-67 promoter activity.Results:GEO and UALCAN database analyses showed that HOXD11 was highly expressed in LSCC(P<0.01).The expressions of HOXD11 and Ki-67 mRNA in LSCC tissues were significantly higher than those in adjacent tissues(both P<0.01).At the same time,there was a positive correlation between the expressions of HOXD11 and Ki-67 mRNA(r=0.26,P<0.05).The expressions of HOXD11 mRNA in LSCC cell lines were significantly higher than those in HNLEC(all P<0.01).HOXD11 knockdown significantly inhibited the proliferation,migration and invasion of LSCC cells(all P<0.01),while HOXD11 overexpression promoted these malignant biological behaviors of LSCC cells(all P<0.01).Both dual-luciferase reporter gene assay and ChIP assay confirmed that HOXD11 could directly bind to the Ki-67 promoter region to regulate its expression(P<0.01).The rescue experiment showed that overexpression of Ki-67 partially reverse the inhibitory effect of HOXD11 knockdown on the proliferation,migration and invasion of LSCC cells(all P<0.01).Conclusion:HOXD11 is highly expressed in LSCC tissues and cell lines.It directly regulates Ki-67 transcriptional activity and promotes the proliferation,migration and invasion of LSCC cells.关键词
喉鳞状细胞癌/同源异型盒蛋白D11/Ki-67/增殖/迁移/侵袭/转录调控Key words
laryngeal squamous cell carcinoma(LSCC)/homeobox D11(HOXD11)/Ki-67/proliferation/migration/invasion/transcriptional regulation分类
医药卫生引用本文复制引用
孔延男,刘亮,刘艳丽,赵惠玲,牛云峰..HOXD11通过转录调控Ki-67活性促进喉鳞状细胞癌细胞的恶性生物学行为[J].中国肿瘤生物治疗杂志,2026,33(4):379-388,10.基金项目
河北省医学科学研究课题计划(20240854) （20240854）
