Yu Hao, Dong Liqian, Wang Hongyu, Zhang Yang, Wang Zhuo, Wang Can, Xia Hong, Bao Huizheng
Department of Hematology, Jilin Cancer Hospital, Changchun, Jilin, 130012, People's Republic of China.
Department of Nephrology, Jilin Province FAW General Hospital, Changchun, Jilin, 130013, People's Republic of China.
Cancer Manag Res. 2021 Feb 22;13:1803-1815. doi: 10.2147/CMAR.S276290. eCollection 2021.
Long intergenic non-protein coding RNA 504 (LINC00504) is a long non-coding RNA that has an important regulatory role in a variety of human cancers. In this study, LINC00504 expression in breast cancer tissues and cell lines was detected. Studies were also conducted to determine the impact of LINC00504 on the tumor behavior of breast cancer cells. The potential mechanisms underlying the oncogenic role of LINC00504 in breast cancer cells were elucidated in detail.
Expression of LINC00504 in breast cancer was analyzed by quantitative real-time polymerase chain reaction. The effects of LINC00504 on proliferation, apoptosis, in vitro migration and invasion, and in vivo tumor growth were elucidated using Cell Counting Kit-8 assay, flow cytometry, Transwell assays, and tumor xenograft models, respectively. Bioinformatics analyses in conjunction with RNA immunoprecipitation, luciferase reporter assays, and rescue experiments were conducted to investigate the underlying molecular mechanisms.
LINC00504 was upregulated in breast cancer tissues and cell lines. Knocking down LINC00504 suppressed breast cancer cell proliferation, migration, and invasion and facilitated apoptosis in vitro. In addition, tumor growth in vivo was significantly inhibited by LINC00504 depletion. Regarding the underlying mechanism, LIN00504 could function as a competing endogenous RNA in breast cancer by sponging microRNA-876-3p (miR-876-3p), resulting in the upregulation of high mobility group box 3 (HMGB3). Rescue experiments further revealed that miR-876-3p downregulation or HMGB3 upregulation effectively reversed the inhibitory effects of LIN00504 deficiency on breast cancer cells.
The LIN00504-miR-876-3p-HMGB3 axis shows carcinogenic effects in modulating the biological behavior of breast cancer cells. This pathway may represent an effective target for CRC diagnosis and anticancer therapy.
长链基因间非编码RNA 504（LINC00504）是一种长链非编码RNA，在多种人类癌症中发挥重要调控作用。本研究检测了LINC00504在乳腺癌组织和细胞系中的表达。还进行了研究以确定LINC00504对乳腺癌细胞肿瘤行为的影响。详细阐明了LINC00504在乳腺癌细胞中致癌作用的潜在机制。
采用定量实时聚合酶链反应分析LINC00504在乳腺癌中的表达。分别使用细胞计数试剂盒-8检测、流式细胞术、Transwell检测和肿瘤异种移植模型阐明LINC00504对增殖、凋亡、体外迁移和侵袭以及体内肿瘤生长的影响。结合生物信息学分析、RNA免疫沉淀、荧光素酶报告基因检测和挽救实验来研究潜在的分子机制。
LINC00504在乳腺癌组织和细胞系中上调。敲低LINC00504可抑制乳腺癌细胞的增殖、迁移和侵袭，并促进体外凋亡。此外,LINC00504缺失显著抑制体内肿瘤生长。关于潜在机制，LINC00504可通过吸附微小RNA-876-3p（miR-876-3p）在乳腺癌中作为竞争性内源RNA发挥作用，导致高迁移率族蛋白B3（HMGB3）上调。挽救实验进一步表明，miR-876-3p下调或HMGB3上调可有效逆转LINC00504缺失对乳腺癌细胞的抑制作用。
LINC00504-miR-876-3p-HMGB3轴在调节乳腺癌细胞生物学行为方面显示出致癌作用。该通路可能是结直肠癌诊断和抗癌治疗的有效靶点。
