Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China.
Oncol Res. 2018 May 7;26(4):625-635. doi: 10.3727/096504017X14953948675395. Epub 2017 May 21.
Breast cancer is a serious threat to women's physical and psychological health. Long noncoding RNA CAMTA1 (lncCAMTA1) was believed to be related with tumor progression, but its role in breast cancer is not clear. The human breast cancer cell line MDA-MB-231 was used to investigate the effect of lncCAMTA1 on cell viability, migration/invasion, and apoptosis. The expression of lncCAMTA1, miR-20b, and in MDA-MB-231 were measured after corresponding transfections. Binding effects between lncCAMTA1 and miR-20b, miR-20b, and VEGF 3'-UTR were measured. The effects of miR-20b and VEGF on breast cancer cells were also assessed after transfections. The phosphorylation levels of the MAPK/ERK and JAK/STAT3 pathways were determined to assess the effect of VEGF. The results showed that lncCAMTA1 expression promoted cell viability and migration/invasion, while knockdown of lncCAMTA1 promoted cell apoptosis via binding with miR-20b. lncCAMTA1 negatively regulated miR-20b expression. VEGF was a target of miR-20b, leading to the modification of the phosphorylation levels of MAPK, ERK, JAK, STAT1, and STAT3. Our findings suggested that lncCAMTA1 might promote proliferation and mobility of human breast cancer cells via binding with miR-20b. VEGF was a direct target of miR-20b and regulated activation of the MAPK/ERK and JAK/STAT3 signaling pathways. Therefore lncCAMTA1 has potential as a novel cancer diagnostic marker and as a putative novel therapeutic target for breast cancer treatment.
乳腺癌是严重威胁女性身心健康的疾病。长链非编码 RNA CAMTA1(lncCAMTA1)被认为与肿瘤进展有关,但它在乳腺癌中的作用尚不清楚。本研究用人乳腺癌 MDA-MB-231 细胞系探讨 lncCAMTA1 对细胞活力、迁移/侵袭和细胞凋亡的影响。转染相应质粒后,检测 lncCAMTA1、miR-20b 和 在 MDA-MB-231 中的表达。检测 lncCAMTA1 与 miR-20b、miR-20b 与 VEGF 3'-UTR 的结合效应。转染后评估 miR-20b 和 VEGF 对乳腺癌细胞的影响。测定 MAPK/ERK 和 JAK/STAT3 通路的磷酸化水平,以评估 VEGF 的作用。结果表明,lncCAMTA1 表达促进细胞活力和迁移/侵袭,而敲低 lncCAMTA1 通过与 miR-20b 结合促进细胞凋亡。lncCAMTA1 负调控 miR-20b 表达。VEGF 是 miR-20b 的靶基因,导致 MAPK、ERK、JAK、STAT1 和 STAT3 磷酸化水平的改变。本研究结果表明,lncCAMTA1 可能通过与 miR-20b 结合促进人乳腺癌细胞的增殖和迁移。VEGF 是 miR-20b 的直接靶基因,调节 MAPK/ERK 和 JAK/STAT3 信号通路的激活。因此,lncCAMTA1 具有作为新型癌症诊断标志物和乳腺癌治疗新的潜在治疗靶点的潜力。