Molecular and Tumor Research Center, The Basic Medical School of Chongqing Medical University, Chongqing 400016, P.R. China.
Int J Oncol. 2023 Oct;63(4). doi: 10.3892/ijo.2023.5559. Epub 2023 Aug 18.
Breast cancer (BRCA) exhibits a high incidence rate among women worldwide. LOC127814295 (ENSG00000232995), termed long non‑coding (lnc)‑regulator of G protein signaling 5 (RGS5), is a novel lncRNA with a genomic region overlapping with protein‑coding gene RGS5. Results obtained using The Cancer Genome Atlas demonstrated that lnc‑RGS5 was deregulated in diverse cancer types, including BRCA; however, the functional role of lnc‑RGS5 remains unclear. Results of the present study demonstrated that lnc‑RGS5 was upregulated in BRCA tissues compared with healthy samples (n=30; P<0.0001), and was associated with the overall survival of patients with triple‑negative BRCA (n=106; P<0.05). Moreover, lnc‑RGS5 expression was significantly higher in triple‑negative BRCA samples than in LumA, LumB, or Her2 subtypes (P<0.05). Functionally, lnc‑RGS5 upregulation promoted BRCA cell proliferation , whereas lnc‑RGS5 knockdown elicited the opposite function. Stable knockdown of lnc‑RGS5 inhibited tumor cell proliferation . Bioinformatics analysis revealed that lnc‑RGS5 was significantly associated with RNA binding involved in post‑transcriptional gene silencing (P=0.002). Mechanistically, lnc‑RGS5 functions as a competing endogenous RNA via competitively sponging miR‑542‑5p to upregulate forkhead box M1 (FoxM1) and the VEGFA/Neuropilin 1 axis; thus, promoting BRCA cell proliferation . Moreover, rescue experiments validated that the lnc‑RGS5/miR‑542‑5p/FoxM1 axis promoted BRCA cell growth . Collectively, results of the present study demonstrated that lnc‑RGS5 may exhibit potential as a novel oncogenic lncRNA in BRCA. The present study may provide a novel theoretical basis for the role of lncRNA in the targeted therapy of BRCA.
乳腺癌（BRCA）在全球女性中发病率较高。LOC127814295（ENSG00000232995），称为 G 蛋白信号调节物 5（RGS5）的长非编码（lnc）RNA，是一种新型 lncRNA，其基因组区域与蛋白编码基因 RGS5 重叠。使用癌症基因组图谱（The Cancer Genome Atlas）获得的结果表明，lnc-RGS5 在多种癌症类型中失调，包括 BRCA；然而，lnc-RGS5 的功能作用尚不清楚。本研究结果表明，lnc-RGS5 在 BRCA 组织中上调，与健康样本（n=30；P<0.0001）相比，与三阴性 BRCA 患者的总生存相关（n=106；P<0.05）。此外，lnc-RGS5 在三阴性 BRCA 样本中的表达显著高于 LumA、LumB 或 Her2 亚型（P<0.05）。功能上，lnc-RGS5 上调促进 BRCA 细胞增殖，而 lnc-RGS5 敲低则产生相反的功能。lnc-RGS5 的稳定敲低抑制肿瘤细胞增殖。生物信息学分析显示，lnc-RGS5 与涉及转录后基因沉默的 RNA 结合显著相关（P=0.002）。在机制上，lnc-RGS5 通过竞争性地吸附 miR-542-5p 作为竞争内源性 RNA，上调叉头框 M1（FoxM1）和血管内皮生长因子 A/神经纤毛蛋白 1 轴，从而促进 BRCA 细胞增殖。此外，验证实验表明，lnc-RGS5/miR-542-5p/FoxM1 轴促进 BRCA 细胞生长。综上所述，本研究表明 lnc-RGS5 可能在 BRCA 中作为一种新型致癌 lncRNA 发挥作用。本研究可能为 lncRNA 在 BRCA 靶向治疗中的作用提供新的理论依据。
