Long non-coding RNA TUSC8 inhibits breast cancer growth and metastasis via miR-190b-5p/MYLIP axis
Long non-coding RNA TUSC8 inhibits breast cancer growth and metastasis via miR-190b-5p/MYLIP axis
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长非编码RNA TUSC8通过miR-190b-5p/MYLIP轴抑制乳腺癌生长和转移
DOI：
10.18632/aging.102791
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发表时间：
2020-02-15
期刊：
影响因子：
5.2
通讯作者：
Mao, Yitao
中科院分区：
文献类型：
--
作者：
Zhao, Luqing;Zhou, Yangying;Mao, Yitao
lncRNA肿瘤抑制因子候选物8（TUSC 8）在几种癌症的发展中起关键作用。然而，TUSC 8与乳腺癌相关的生物学功能和潜在的分子机制在很大程度上仍不清楚。在这里，我们发现TUSC 8在乳腺癌组织中显著下调，其高表达预示着乳腺癌患者的预后更好。在功能上，TUSC 8的敲低在体外显著促进乳腺癌细胞的增殖、迁移和侵袭，并且在体内促进致瘤性和转移。荧光素酶报告基因、RIP和RNA pull-down分析的结果证明TUSC 8对miR-190 b-5 p具有分子海绵的功能。此外，我们发现TUSC 8通过与miR-190 b-5 p竞争性结合作为肌球蛋白调节轻链相互作用蛋白（MYLIP）的竞争性内源性RNA（ceRNA），并通过调节上皮-间质转化（EMT）相关标志物的表达来抑制乳腺癌转移。临床上，受试者工作特征曲线（ROC）分析显示，TUSC 8和MYLIP的联合使用可能成为新的有前途的乳腺癌诊断生物标志物。综上所述，这些结果表明TUSC 8通过miR-190 b-5 p/MYLIP轴抑制乳腺癌的生长和转移，为我们开发乳腺癌患者的潜在治疗靶点提供了新的见解。
The lncRNA tumor suppressor candidate 8 (TUSC8) plays a critical role in the development of several cancers. However, the biological functions and underlying molecular mechanisms of TUSC8 with respect to breast cancer remain largely unclear. Here, we found that TUSC8 was significantly down-regulated in breast cancer tissues and its high expression predicted better prognosis of breast cancer patients. Functionally, knock-down of TUSC8 drastically promoted the proliferation, migration and invasion of breast cancer cells in vitro and facilitated tumorigenicity and metastasis in vivo. Mechanistically, the results of luciferase reporter, RIP and RNA pull-down assays proved that TUSC8 functioned as molecular sponge for miR-190b-5p. Furthermore, we showed that TUSC8 served as a competing endogenous RNA (ceRNA) of myosin regulatory light chain interacting protein (MYLIP) through competitively binding with miR-190b-5p and suppressed breast cancer metastasis through regulating the expression of epithelial–mesenchymal transition (EMT) related markers. Clinically, the receiver operating characteristic curve (ROC) analyses revealed that the combination usage of TUSC8 and MYLIP might become novel promising diagnostic biomarkers for breast cancer. Taken together, these results suggested that TUSC8 inhibited breast cancer growth and metastasis via miR-190b-5p/MYLIP axis, providing us new insights into developing potential therapeutic targets for breast cancer patients.