Section of Oncology, Department of Clinical Science, University of Bergen, Bergen, Norway.
Department of Biomedicine, University of Bergen, Bergen, Norway.
Mol Cancer Res. 2018 Jan;16(1):78-89. doi: 10.1158/1541-7786.MCR-17-0207. Epub 2017 Oct 11.
Transcripts derived from the function as decoys to adsorb miRNAs targeting the tumor suppressor for degradation, and upregulation is known to inhibit growth in preclinical cancer models. Here, 3'UTR transduction influences PTEN, AKT/mTOR signaling, and tumor progression in estrogen receptor (ER)-positive and -negative breast cancer cells. upregulation decreases gene expression in the ER-positive MCF7 and T47D human breast carcinoma cells and accelerates MCF7 tumor growth Of note, transduction significantly decreases ERα () mRNA and protein levels in MCF7 xenografts with a concomitant increase in hsa-miR-26a, a miRNA known to target In the ER-negative MDA-MB-231 and C3HBA breast cancer cells, upregulation of increases gene expression with no influence on hsa-miR-26a, , or ERα expression. While transduction did not influence the growth rate of human MDA-MB-231 xenografts, upregulation profoundly reduces its metastatic propensity. Furthermore, significantly inhibits the growth rate of ER-negative C3HBA murine breast cancer xenografts. transduction had no influence on doxorubicin cytotoxicity in ER-positive MCF7 cells but an increase in doxorubicin sensitivity was observed in the ER-negative MDA-MB-231 cells. In summary, while upregulation decreased transcript levels and stimulated the growth of ER-positive breast cancers, increased transcript levels and inhibited tumor progression was observed in the ER-negative cells. This report highlights the profound biological activity of in breast cancer, which is dictated by the hormone receptor status. .
从功能上转录而来的 RNA 可作为诱饵来吸附针对肿瘤抑制因子的 miRNA，从而导致其降解，而上调则已知可抑制临床前癌症模型中的生长。在这里，3'UTR 转导影响 PTEN、AKT/mTOR 信号通路和雌激素受体（ER）阳性和阴性乳腺癌细胞的肿瘤进展。上调可降低 ER 阳性 MCF7 和 T47D 人乳腺癌细胞中的基因表达，并加速 MCF7 肿瘤生长。值得注意的是，转导显著降低了 MCF7 异种移植瘤中 ERα（）mRNA 和蛋白水平，同时增加了 hsa-miR-26a 的表达，该 miRNA 已知可靶向。在 ER 阴性 MDA-MB-231 和 C3HBA 乳腺癌细胞中，上调可增加基因表达，而对 hsa-miR-26a、或 ERα 表达没有影响。虽然转导对人 MDA-MB-231 异种移植瘤的生长速度没有影响，但上调可显著降低其转移倾向。此外，还显著抑制了 ER 阴性 C3HBA 鼠乳腺癌异种移植瘤的生长速度。转导对 ER 阳性 MCF7 细胞中的阿霉素细胞毒性没有影响，但在 ER 阴性 MDA-MB-231 细胞中观察到阿霉素敏感性增加。总之，上调虽然降低了 ER 阳性乳腺癌中的转录水平并刺激其生长，但在 ER 阴性细胞中观察到增加的转录水平并抑制了肿瘤进展。本报告强调了在乳腺癌中 的深远生物学活性，这取决于激素受体状态。
