中国癌症防治杂志2026，Vol.18Issue(1)：77-86,10.DOI:10.3969/j.issn.1674-5671.2026.01.10
长链非编码RNA KAZALD1-1在肝细胞癌中的表达及其对肝癌细胞生物学行为的影响
Expression of the long non-coding RNA KAZALD1-1 in hepatocellular carcinoma and its impact on the biological behavior of liver cancer cells
摘要
Abstract
Objective Hepatocellular carcinoma(HCC)is characterized by high malignancy,rapid progression,and poor survival rates.It is imperative to identify biomarkers for diagnosing HCC and predicting patient prognosis.Extensive research indicates that long non-coding RNAs(lncRNAs)play a crucial regulatory roles in the initiation and progression of HCC,thereby influencing patient outcomes.This study aims to investigate the expression of lncRNA Kazal type serine peptidase inhibitor domain 1 transcript variant 1(KAZALD1-1)in HCC,evaluate its effects of cell proliferation,invasion,migration,cell cycle progression,and apoptosis in liver cancer cells,and explore its associated competitive endogenous RNA(ceRNA)network.Methods Five pairs of HCC tumor and matched adjacent non-tumor tissues were collected from patients undergoing liver resection at the Guangxi Medical University Cancer Hospital in October 2019.Whole-transcriptome sequencing data were analyzed to identify the significantly upregulated lncRNA KAZALD1-1 in HCC tissues.Tumor and matched adjacent non-tumor tissues were collected from 105 HCC patients who underwent liver resection at the hospital between October 2018 and November 2022.The expression levels of lncRNA KAZALD1-1 were detected by quantita-tive reverse transcription polymerase chain reaction(qRT-PCR).The differential expression of this lncRNA and its impact on overall survival(OS)in HCC patients were evaluated using data from The Cancer Genome Atlas(TCGA)database.Stable knockdown and overexpression cell lines of lncRNA KAZALD1-1 were established in the liver cancer cell lines Huh7,HCCLM3,and SNU449.The effects of lncRNA KAZALD1-1 on liver cancer cell proliferation,migration,invasion,cell cycle progression,and apoptosis were evaluated using Cell Counting Kit-8(CCK-8)assays,scratch assays,Transwell assays,and flow cytometry,respectively.Furthermore,the TCGA database was utilized to explore the ceRNA network associated with lncRNA KAZALD1-1.Results Bioinformatics analysis of sequencing data and the TCGA database demonstrated that lncRNA KAZALD1-1 was upregulated in HCC tissues,with its elevated expression was significantly associated with the reduced OS in HCC patients(all P<0.05).qRT-PCR results confirmed that lncRNA KAZALD1-1 was significantly overexpressed in HCC tissues compared to adjacent non-cancerous tissues.Patients with high lncRNA KAZALD1-1 expression exhibited significantly poorer OS than those with lower expression levels.Further analysis using Cox proportional hazards regression identified high lncRNA KAZALD1-1 expression as an independent risk factor for poor prognosis in HCC patients.Sub-group analysis results indicated that high lncRNA KAZALD1-1 expression was associated with reduced OS in HCC patients aged≥54 years,those without cirrhosis,AFP≤400 ng/mL those presenting with solitary tumors,intact tumor capsules,absence of satellite nodules,and those classified as Edmondson stage Ⅰ-Ⅱ(all P<0.05).In vitro experiments demonstrated that knockdown of lncRNA KAZALD1-1 inhib-ited proliferation,migration,and invasion in Huh7 and HCCLM3 cells,while delaying cell cycle progression and promoting cell apoptosis(all P<0.05).Conversely,overexpression of lncRNA KAZALD1-1 enhanced proliferation,migration,and invasion in Huh7 and SNU449 cells,accelerated cell cycle progression and suppressed cell apoptosis(all P<0.05).The constructed ceRNA network indicated that hsa-miR-21028 and SC65 may serve as potential regulatory targets for lncRNA KAZALD1-1 in HCC progression.Conclusions LncRNA KAZALD1-1 is significantly overexpressed in HCC tissues and is associated with reduced OS rates in affected patients.It may promote HCC proliferation,invasion,and migration through the lncRNA KAZALD1-1/hsa-miR-21028/SC65 axis,accelerate cell cycle progression,and suppress cell apoptosis.关键词
长链非编码RNA KAZALD1-1/肝细胞癌/增殖/迁移/侵袭Key words
Long non-coding RNA KAZALD1-1/Hepatocellular carcinoma/Proliferation/Migration/Invasion分类
医药卫生引用本文复制引用
谭力铮,莫秋燕,周子寒,李科志,余红平,温秋萍..长链非编码RNA KAZALD1-1在肝细胞癌中的表达及其对肝癌细胞生物学行为的影响[J].中国癌症防治杂志,2026,18(1):77-86,10.基金项目
国家自然科学基金地区科学基金项目(82460668) （82460668）
广西自然科学基金重点项目区域高发疾病研究联合专项(2024GXNSFDA010040) （2024GXNSFDA010040）
广西区域性高发肿瘤早期防治研究重点实验室自主研究项目(GKE-ZZ202316) （GKE-ZZ202316）
111项目(D17011) （D17011）
广西自然科学基金青年科学基金项目(2025GXNSFBA069144) （2025GXNSFBA069144）
广西科技基地和人才专项(桂科AD25069077) （桂科AD25069077）
