南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (4): 544-551.doi: 10.12122/j.issn.1673-4254.2023.04.06

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HSDL2高表达促进直肠癌细胞增殖：基于激活CDK6/cyclinD1信号通路

程 阳，何旭旭，王 炼，许轶博，沈梦迪，张文静，夏勇生，张 婕，张 敏，王宜君，胡建国，张 军   

  1. 蚌埠医学院第一附属医院输血科，胃肠外科，消化内科，检验科，安徽 蚌埠 233004；蚌埠医学院，安徽 蚌埠 233000；蚌埠医学院组织移植重点实验室，安徽 蚌埠 233030
  • 出版日期:2023-04-20 发布日期:2023-05-15

HSDL2 overexpression promotes rectal cancer progression by regulating cancer cell cycle and promoting cell proliferation

CHENG Yang, HE Xuxu, WANG Lian, XU Yibo, SHEN Mengdi, ZHANG Wenjing, XIA Yongsheng, ZHANG Jie, ZHANG Min, WANG Yijun, HU Jianguo, ZHANG Jun   

  1. Department of Blood Transfusion, Department of Gastrointestinal Surgery, Department of Gastroenterology, Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; Bengbu Medical College, Bengbu 233000, China; Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu 233030, China
  • Online:2023-04-20 Published:2023-05-15

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摘要： 目的 明确羟基类固醇脱氢酶样蛋白2（HSDL2）在直肠癌组织中的表达及对癌细胞增殖能力的影响。方法 基于前瞻性临床数据库和生物标本库系统分析2020年1月~2022年6月我院收治的90例直肠癌患者的临床资料。采用免疫组化法检测90例直肠癌组织与癌旁组织中HSDL2的表达水平。根据HSDL2表达中位数分为高表达组（n=45）与低表达组（n=45），分析其与肿瘤临床病理参数间的关系。基于GEO数据库，对HSDL2进行GO功能注释和KEGG通路富集，分析HSDL2在直肠癌中潜在的生物学功能和作用机制；分别采用慢病毒NC、Si-HSDL2与LV-HSDL2转染SW480细胞，CCK8法检测各组细胞增殖能力，流式细胞术检测HSDL2对细胞周期的影响，免疫印迹法检测细胞周期相关蛋白的表达。结果 直肠癌组织中HSDL2的表达水平显著高于癌旁组织（P<0.05）。Spearman相关性分析显示HSDL2、Ki67蛋白与血CEA、血CA19-9水平均呈正相关（P<0.01）。HSDL2高表达组患者的T3-4期、N2-3期、血CEA≥5 μg/L与血CA19-9≥37 kU/L比例明显高于低表达组（P<0.05）。GO分析显示HSDL2主要富集到DNA复制等生物学过程。KEGG富集显示HSDL2主要参与细胞周期等信号通路。上调HSDL2表达显著促进SW480细胞的体外增殖能力（P<0.05），同时促进S期细胞比例（P<0.05）与细胞周期相关蛋白CDK6、CyclinD1的表达（P<0.05）；下调HSDL2则抑制细胞增殖、S期细胞比例与CDK6、CyclinD1的表达（P<0.05）。结论 HSDL2在直肠癌组织中高表达，与直肠癌恶性进展相关，并促进直肠癌细胞增殖能力，影响细胞周期进程。

关键词: 直肠癌；HSDL2；细胞增殖；细胞周期；生物标志物

Abstract: Objective To analyze the expression of hydroxysteroid dehydrogenase like 2 (HSDL2) in rectal cancer tissues and the effect of changes in HSDL2 expression level on proliferation of rectal cancer cells. Methods Clinical data and tissue samples of 90 patients with rectal cancer admitted to our hospital from January 2020 to June 2022 were collected from the prospective clinical database and biological specimen database. The expression level of HSDL2 in rectal cancer and adjacent tissues was detected by immunohistochemistry, and based on the median level of HSDL2 expression, the patients were divided into high expression group (n=45) and low expression group (n=45) for analysis the correlation between HSDL2 expression level and the clinicopathological parameters. GO and KEGG enrichment analyses were performed to explore the role of HSDL2 in rectal cancer progression. The effects of changes in HSDL2 expression levels on rectal cancer cell proliferation, cell cycle and protein expressions were investigated in SW480 cells with lentivirus-mediated HSDL2 silencing or HSDL2 overexpression using CCK-8 assay, flow cytometry and Western blotting. Results The expressions of HSDL2 and Ki67 were significantly higher in rectal cancer tissues than in the adjacent tissues (P<0.05). Spearman correlation analysis showed that the expression of HSDL2 protein was positively correlated with Ki67, CEA and CA19-9 expressions (P<0.01). The rectal cancer patients with high HSDL2 expressions had significantly higher likelihood of having CEA ≥5 μg/L, CA19-9 ≥37 kU/L, T3-4 stage, and N2-3 stage than those with a low HSDL2 expression (P<0.05). GO and KEGG analysis showed that HSDL2 was mainly enriched in DNA replication and cell cycle. In SW480 cells, HSDL2 overexpression significantly promoted cell proliferation, increased cell percentage in S phase, and enhanced the expression levels of CDK6 and cyclinD1 (P<0.05), and HSDL2 silencing produced the opposite effects (P<0.05). Conclusion The high expression of HSDL2 in rectal cancer participates in malignant progression of the tumor by promoting the proliferation and cell cycle progress of the cancer cells.

Key words: rectal cancer; HSDL2; cell proliferation; cell cycle; biomarkers