| 闫 军,周高晋,马曙涛,米尔夏提·米吉提,帕合热迪尼,马 博.外泌体lncRNA TTN-AS1通过miR-524-5p介导TGFβ/Smads通路调控乳腺癌进展的机制研究[J].现代生物医学进展英文版,2024,(15):2845-2849. |
| 外泌体lncRNA TTN-AS1通过miR-524-5p介导TGFβ/Smads通路调控乳腺癌进展的机制研究 |
| Extracellular lncRNA TTN-AS1 Mediates miR-524-5p through TGFβ/Smads Pathway Regulating the Progress of Breast Cancer |
| Received:November 10, 2023 Revised:November 30, 2023 |
| DOI：10.13241/j.cnki.pmb.2024.15.007 |
| 中文关键词: 乳腺癌 lncRNA TTN-AS1 miR-524-5p 转化生长因子β 信号通路 增殖 凋亡 |
| 英文关键词: Breast cancer LncRNA TTN-AS1 MiR-524-5p Transforming growth factor β Signal pathway Proliferation Apoptosis |
| 基金项目:新疆维吾尔自治区自然科学基金项目(2022 D01A137) |
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| 中文摘要: |
| 摘要 目的：探讨外泌体长链非编码RNA（lncRNA ）TTN-AS1通过miR-524-5p介导转化生长因子β（TGFβ）/Smads信号通路，进而调控乳腺癌进展的分子机制。方法：首先采用实时荧光定量聚合酶链反应（qRT-PCR）检测人乳腺癌细胞MDA-MB-231、MCF-7、SKBR-3和乳腺上皮细胞MCF-10A中lncRNA TTN-AS1和miR-524-5p表达量，Western blot法检测TGFβ1和p-Smad2蛋白的表达量。然后采用细胞转染技术抑制lncRNA TTN-AS1表达，比较MDA-MB-231（阴性对照）和转染组lncRNA TTN-AS1、miR-524-5p、TGFβ1和p-Smad2表达量。CCK8法检测细胞增殖力，流式细胞术检测凋亡率，Transwell小室检测迁移力。结果：与MCF-10A相比，MDA-MB-231、 MCF-7和SKBR-3中lncRNA TTN-AS1表达量显著升高，而miR-524-5p明显下降，TGFβ1和p-Smad2上调（P＜0.05）。与阴性对照相比，转染组lncRNA TTN-AS1表达量显著降低，而miR-524-5p明显增加，TGFβ1和p-Smad2下调（P＜0.05）。细胞增殖率和迁移细胞数目明显下降，而凋亡率增加（P＜0.05）。结论：lncRNA TTN-AS1在乳腺癌的进展中可能发挥促癌效应，通过抑制miR-524-5p表达并激活TGFβ1/Smad2信号通路活性来参与调控乳腺癌的增殖与凋亡。lncRNA TTN-AS1有望成为靶向干预乳腺癌的新型分子位点。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the molecular mechanism of extracellular long chain non coding RNA (lncRNA) TTN-AS1 mediated miR-524-5p through transforming growth factor β (TGF β/Smads signaling pathway, then to regulate the breast cancer progression. Methods: Firstly, real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expressions of lncRNA TTN-AS1 and miR-524-5p in human breast cancer cell MDA-MB-231, MCF-7, SKBR-3 and breast epithelial cell MCF-10A, Western blot was to detect TGF β1 and p-Smad2 proteins expression. Then, cell transfection technology was used to inhibit expression of lncRNA TTN-AS1, lncRNA TTN-AS1, miR-524-5p, TGFβ1 and p-Smad2 expressions were compared between MDA-MB-231 (negative control) and transfection group. CCK8 method was to detect cell proliferation, flow cytometry was to detect cell apoptosis rate, and Transwell chamber was to detect cell migration. Results: Compared with MCF-10A, the expression levels of lncRNA TTN-AS1 in MDA-MB-231, MCF-7, SKBR-3 were significantly higher, while miR-524-5p were significantly less, TGFβ1 and p-Smad2 were upregulated (P<0.05). Compared with the negative control group, the expressions of lncRNA TTN-AS1 in the transfection group was significantly lower, while miR-524-5p was significantly more, resulting in TGF β1 and p-Smad2 were downregulated (P<0.05). The cell proliferation rate and the number of migrating cells were significantly less, while the apoptosis rate was higher (P<0.05). Conclusion: lncRNA TTN-AS1 may play a cancer promoting role in the progression of breast cancer by inhibiting the expression of miR-524-5p and activating TGF β1/Smad2 signaling pathway, which is involved in regulating the proliferation and apoptosis of breast cancer. LncRNA TTN-AS1 is expected to become a new molecular site targeting breast cancer intervention. |
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