Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
Department of Pathology, School of Basic Medical Science, Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, China.
Aging (Albany NY). 2020 Feb 9;12(3):2974-2991. doi: 10.18632/aging.102791.
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 and facilitated tumorigenicity and metastasis . 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.
长链非编码 RNA 肿瘤抑制候选基因 8（TUSC8）在多种癌症的发生发展中发挥着关键作用。然而，TUSC8 与乳腺癌的生物学功能和潜在分子机制在很大程度上仍不清楚。在这里，我们发现 TUSC8 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较好。功能上，TUSC8 的敲低显著促进了乳腺癌细胞的增殖、迁移和侵袭，并促进了肿瘤发生和转移。在机制上，荧光素酶报告、RIP 和 RNA 下拉实验的结果证明了 TUSC8 作为 miR-190b-5p 的分子海绵发挥作用。此外，我们表明 TUSC8 通过竞争性结合 miR-190b-5p 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-间充质转化（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）分析表明，TUSC8 和 MYLIP 的联合使用可能成为乳腺癌新的有前途的诊断生物标志物。总之，这些结果表明，TUSC8 通过 miR-190b-5p/MYLIP 轴抑制乳腺癌的生长和转移，为开发乳腺癌患者的潜在治疗靶点提供了新的见解。
