Oncology Institute, Affiliated Hospital of Jiangnan University, Wuxi 214062, China.
Department of Oncological Surgery, Affiliated Hospital of Jiangnan University, Wuxi 214062, China.
Biomed Res Int. 2020 Apr 11;2020:9747826. doi: 10.1155/2020/9747826. eCollection 2020.
Understanding of prognostic factors and therapeutic targets for breast cancer is imperative for guidance of patient care. We studied 1203 tumour samples from the Gene Expression Omnibus (GEO) to evaluate potential genes related to breast cancer. R software was used to analyse differentially expressed long noncoding RNAs (lncRNAs) in the RNA microarray expression profiles GSE45827 and GSE65216 and to identify a series of differentially expressed lncRNAs associated with human breast cancer. Of these lncRNAs, A2M-AS1, a lncRNA that has not been previously reported, was significantly upregulated in human breast cancer tissues compared with adjacent nontumour tissues. Importantly, A2M-AS1 upregulation was significantly associated with ER-negative, HER2-positive, and basal-like breast cancer and with poor recurrence-free survival and metastasis-free survival in breast cancer patients. After validating these results in 96 collected human breast cancer tissues and 64 paired adjacent noncancerous tissues, we further investigated the roles of A2M-AS1 in human ER-negative and basal-like breast cancer cells. The results revealed that A2M-AS1 significantly promotes human breast cancer cell proliferation, invasion, and migration. Additionally, bioinformatics analysis of genes coexpressed with A2M-AS1 in the context of human breast cancer combined with qRT-PCR and Western blot assays revealed that A2M-AS1 exerts regulatory effects on downstream factors in the cell adhesion molecule pathway, including CD2 and SELL. These results imply that A2M-AS1 might be a promising candidate prognostic factor and therapeutic target for breast cancer.
了解乳腺癌的预后因素和治疗靶点对于指导患者护理至关重要。我们研究了来自基因表达综合数据库（GEO）的 1203 个肿瘤样本，以评估与乳腺癌相关的潜在基因。使用 R 软件分析了 RNA 微阵列表达谱 GSE45827 和 GSE65216 中差异表达的长非编码 RNA（lncRNA），并确定了一系列与人类乳腺癌相关的差异表达 lncRNA。在这些 lncRNA 中，A2M-AS1 是一种以前未报道过的 lncRNA，在人类乳腺癌组织中明显上调，与相邻非肿瘤组织相比。重要的是，A2M-AS1 的上调与 ER 阴性、HER2 阳性和基底样乳腺癌显著相关，并且与乳腺癌患者的无复发生存和无转移生存不良相关。在 96 例收集的人类乳腺癌组织和 64 对配对的相邻非癌组织中验证这些结果后，我们进一步研究了 A2M-AS1 在人类 ER 阴性和基底样乳腺癌细胞中的作用。结果表明，A2M-AS1 显著促进人类乳腺癌细胞的增殖、侵袭和迁移。此外，对与人类乳腺癌中 A2M-AS1 共表达的基因进行生物信息学分析，并结合 qRT-PCR 和 Western blot 分析，结果表明 A2M-AS1 对细胞黏附分子途径中的下游因子（包括 CD2 和 SELL）发挥调节作用。这些结果表明，A2M-AS1 可能是一种有前途的候选预后因素和治疗靶点，用于乳腺癌。
