Department of General Surgery, 627662The Affiliated Jiangsu Shengze Hospital of Nanjing Medical University, Suzhou, Jiangsu, China.
Neonatal Department, 604074Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China.
Technol Cancer Res Treat. 2023 Jan-Dec;22:15330338231164359. doi: 10.1177/15330338231164359.
Emerging evidence suggests that long noncoding RNAs (lncRNAs) play an important role in the progression of multiple human cancers including breast cancer. In this study, we aimed to research novel functions of long intergenic noncoding RNA 460 (LINC00460) on cell proliferation and ferroptosis in breast cancer. UALCAN, TANRIC, and GSE16446 data were used to analyze the expression of LINC00460 in breast cancer tissues. Furthermore, real-time quantitative PCR, western blot, cell proliferation assay, iron assay, and malondialdehyde (MDA) assay were applied to detect the function and mechanism of particular molecules. The LINC00460 expression was significantly increased in breast cancer tissues compared with normal tissues. Importantly, patients with high LINC00460 expression showed a longer overall survival rate. LINC00460 knockdown markedly suppressed the proliferation of breast cancer cells and promoted ferroptosis. Mechanistic analysis revealed that LINC00460 promoted myelin and lymphocyte protein 2 (MAL2) expression by sponging miR-320a. Moreover, both miR-320a knockdown and MAL2 overexpression could reverse the effects of LINC00460 silencing on cell proliferation and ferroptosis. In summary, our results reveal an alternative mechanism by which breast cancer cells can acquire resistance to ferroptosis via the LINC00460/miR-320a/MAL2 axis.
越来越多的证据表明，长非编码 RNA（lncRNA）在多种人类癌症（包括乳腺癌）的进展中发挥着重要作用。在这项研究中，我们旨在研究长基因间非编码 RNA 460（LINC00460）在乳腺癌细胞增殖和铁死亡中的新功能。UALCAN、TANRIC 和 GSE16446 数据用于分析乳腺癌组织中 LINC00460 的表达。此外，实时定量 PCR、western blot、细胞增殖测定、铁测定和丙二醛（MDA）测定用于检测特定分子的功能和机制。与正常组织相比，LINC00460 在乳腺癌组织中的表达明显增加。重要的是，LINC00460 高表达的患者总生存率更长。LINC00460 敲低显著抑制乳腺癌细胞的增殖并促进铁死亡。机制分析表明，LINC00460 通过海绵吸附 miR-320a 促进髓鞘和淋巴细胞蛋白 2（MAL2）的表达。此外，miR-320a 敲低和 MAL2 过表达均可逆转 LINC00460 沉默对细胞增殖和铁死亡的影响。总之，我们的结果揭示了乳腺癌细胞通过 LINC00460/miR-320a/MAL2 轴获得对铁死亡抗性的另一种机制。
