tRF-Leu通过调控BIRC5逆转乳腺癌细胞化疗耐药

2024年9月，常州市**人民医院，苏州大学第三附属医院肝胆胰外科；南京医科大学附属常州市第二人民医院普外科；大连医科大学研究生院；南京医科大学附属儿童医院 (Hepatopancreatobiliary Surgery Department,The Third Afliated Hospital of Soochow University, Changzhou First People’s Hospital, Changzhou, China.Department of General Surgery, The Afliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, China.   Department Graduate School of Dalian Medical University, Dalian Medical University, Dalian, China.Children’s Hospital of Nanjing Medical University, Nanjing, China.) DongLin

Sun老师研究团队在《Discover Oncology》上发表论文：

“tRF-Leu reverse breast cancer cells chemoresistance by regulation of BIRC5”

“tRF-Leu通过调控BIRC5逆转乳腺癌细胞化疗耐药”

Abstract：

Objective

Accumulating studies reported the crucial roles of tRFs in tumorigenesis. However, their further mechanisms and clinical values remains unclear. This study aimed at the further investigation of tRF-Leu in breast cancer chemotherapy resistance.

Methods

The high-throughput sequencing was performed and identified the downregulation of tRF-Leu in MCF7/ADR cells. The function of tRF-Leu in breast cancer cells and breast cancer chemotherapy resistance was investigated in vitro and in vivo, including colony formation assay, CCK-8 assay, transwell assay and apoptosis assay. The binding site of tRF-Leu on BIRC5 was verified by dual-luciferase assay.

Results

tRF-Leu was downregulated in MCF7/ADR cells. Overexpression of tRF-Leu inhibited the migration of breast cancer cells. Furthermore, tRF-Leu could reverse the resistance of MCF7/ADR cells to Adriamycin both in vitro and in vivo. BIRC5 was a target of tRF-Leu, which might be involved in the chemotherapy resistance regulation.

Conclusion

We demonstrated that tRF-Leu could inhibit the chemotherapy resistance of breast cancer by targeting BIRC5. These findings might identify new biomarkers of breast cancer therapy and bring new strategies to reverse chemotherapy resistance.

摘要：

目的：

越来越多的研究报道了tRFs在肿瘤发生中的关键作用。然而，其进一步的机制和临床价值尚不清楚。本研究旨在进一步探讨tRF-Leu在乳腺癌化疗耐药中的作用。

方法：

对MCF7/ADR细胞进行高通量测序，发现tRF-Leu下调。通过集落形成实验、CCK-8实验、transwell实验和细胞凋亡实验，研究了tRF-Leu在乳腺癌细胞中的作用和乳腺癌化疗耐药性。双荧光素酶实验证实了tRF-Leu在BIRC5上的结合位点。

结果：

tRF-Leu在MCF7/ADR细胞中下调。过表达tRF-Leu可抑制乳腺癌细胞的迁移。此外，tRF-Leu在体外和体内均能逆转MCF7/ADR细胞对阿霉素的耐药。BIRC5是tRF-Leu的靶点，可能参与了化疗耐药的调控。

结论：

我们证明了tRF-Leu可以通过靶向BIRC5抑制乳腺癌的化疗耐药。这些发现可能会发现新的乳腺癌治疗生物标志物，并为逆转化疗耐药带来新的策略。

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