tRNA-Derived Fragment tRF-17-79MP9PP Attenuates Cell Invasion and Migration via THBS1/TGF-β1/Smad3 Axis in Breast Cancer.
tRNA-Derived Fragment tRF-17-79MP9PP Attenuates Cell Invasion and Migration via THBS1/TGF-β1/Smad3 Axis in Breast Cancer.
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tRNA 衍生片段 tRF-17-79MP9PP 通过 THBS1/TGF-b1/Smad3 轴减弱乳腺癌中的细胞侵袭和迁移
DOI：
10.3389/fonc.2021.656078
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发表时间：
2021
影响因子：
4.7
通讯作者：
Yan F
中科院分区：
文献类型：
--
作者：
Mo D;He F;Zheng J;Chen H;Tang L;Yan F
tRNA衍生物已被确定为一种新型的潜在癌症生物标志物。前期研究通过高通量测序技术鉴定出乳腺癌组织中存在30种差异表达的tRNA衍生物。本研究旨在探讨tRNA衍生物在乳腺癌细胞中可能的生物学功能和机制。本研究筛选了一种这样的 tRF，即 tRF-17-79MP9PP (tRF-17) 的 5’-tRF 片段，该片段由成熟的 tRNA-Val-AAC 和 tRNA-Val-CAC 加工而成。 tRF-17在乳腺癌组织和血清中显着低表达。 tRF-17 水平可区分乳腺癌与健康对照，敏感性为 70.4%，特异性为 68.4%。 tRF-17 的过度表达抑制了细胞的恶性活动。 THBS1（Thrombospondin-1）作为 tRF-17 的下游靶标，THBS1 表达的减少也部分恢复了 tRF-17 抑制对乳腺癌细胞活力、侵袭和迁移的影响。此外，tRF-17过表达细胞中THBS1、TGF-β1、Smad3、p-Smad3以及上皮间质转化相关基因N-cadherin、MMP3、MMP9显着下调。此外，tRF-17 减弱了乳腺癌细胞中 THBS1 介导的 TGF-β1/Smad3 信号通路。总的来说，tRF-17/THBS1/TGF-β1/smad3轴阐明了乳腺癌细胞侵袭和迁移的分子机制，并可能成为乳腺癌的潜在治疗靶点。
tRNA derivatives have been identified as a new kind of potential biomarker for cancer. Previous studies have identified that there were 30 differentially expressed tRNAs derivatives in breast cancer tissue with the high-throughput sequencing technique. This study aimed to investigate the possible biological function and mechanism of tRNA derivatives in breast cancer cells. One such tRF, a 5’-tRF fragment of tRF-17-79MP9PP (tRF-17) was screened in this study, which is processed from the mature tRNA-Val-AAC and tRNA-Val-CAC. tRF-17 with significantly low expression in breast cancer tissues and serum. The level of tRF-17 differentiated breast cancer from healthy controls with sensitivity of 70.4% and specificity of 68.4%. Overexpression of tRF-17 suppressed cells malignant activity. THBS1 (Thrombospondin-1) as a downstream target of tRF-17, and reduction of THBS1 expression also partially recovered the effects of tRF-17 inhibition on breast cancer cell viability, invasion and migration. Besides, THBS1, TGF-β1, Smad3, p-Smad3 and epithelial-to-mesenchymal transition related genes N-cadherin, MMP3, MMP9 were markedly down-regulated in tRF-17 overexpressing cells. Moreover, tRF-17 attenuated the THBS1-mediated TGF-β1/Smad3 signaling pathway in breast cancer cells. In general, the tRF-17/THBS1/TGF-β1/smad3 axis elucidates the molecular mechanism of breast cancer cells invasion and migration and could lead to a potential therapeutic target for breast cancer.
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影响因子：
4
作者：
Li P;Xu T;Zhou X;Liao L;Pang G;Luo W;Han L;Zhang J;Luo X;Xie X;Zhu K
通讯作者：
Zhu K
影响因子：
13.6
作者：
Nakagawa, T;Lan, HY;Sautin, YY
通讯作者：
Sautin, YY
DOI：
10.1080/01635581.2014.853087
发表时间：
2014-01-01
影响因子：
2.9
作者：
Choi, Jae Ho;Hwang, Yong Pil;Jeong, Hye Gwang
通讯作者：
Jeong, Hye Gwang
影响因子：
2.7
作者：
Li, Yue-Feng;Pei, Fu-Lai;Cao, Ming-Zheng
通讯作者：
Cao, Ming-Zheng
影响因子：
7.5
作者：
Cui W;Zhou J;Dehne N;Brüne B
通讯作者：
Brüne B