tRF-Leu通過調(diào)控BIRC5逆轉(zhuǎn)乳腺癌細(xì)胞化療耐藥

2024年9月，常州市**人民醫(yī)院，蘇州大學(xué)第三附屬醫(yī)院肝膽胰外科；南京醫(yī)科大學(xué)附屬常州市第二人民醫(yī)院普外科；大連醫(yī)科大學(xué)研究生院；南京醫(yī)科大學(xué)附屬兒童醫(yī)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老師研究團(tuán)隊(duì)在《Discover Oncology》上發(fā)表論文：

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

“tRF-Leu通過調(diào)控BIRC5逆轉(zhuǎn)乳腺癌細(xì)胞化療耐藥”

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：

越來越多的研究報(bào)道了tRFs在腫瘤發(fā)生中的關(guān)鍵作用。然而，其進(jìn)一步的機(jī)制和臨床價(jià)值尚不清楚。本研究旨在進(jìn)一步探討tRF-Leu在乳腺癌化療耐藥中的作用。

方法：

對MCF7/ADR細(xì)胞進(jìn)行高通量測序，發(fā)現(xiàn)tRF-Leu下調(diào)。通過集落形成實(shí)驗(yàn)、CCK-8實(shí)驗(yàn)、transwell實(shí)驗(yàn)和細(xì)胞凋亡實(shí)驗(yàn)，研究了tRF-Leu在乳腺癌細(xì)胞中的作用和乳腺癌化療耐藥性。雙熒光素酶實(shí)驗(yàn)證實(shí)了tRF-Leu在BIRC5上的結(jié)合位點(diǎn)。

結(jié)果：

tRF-Leu在MCF7/ADR細(xì)胞中下調(diào)。過表達(dá)tRF-Leu可抑制乳腺癌細(xì)胞的遷移。此外，tRF-Leu在體外和體內(nèi)均能逆轉(zhuǎn)MCF7/ADR細(xì)胞對阿霉素的耐藥。BIRC5是tRF-Leu的靶點(diǎn)，可能參與了化療耐藥的調(diào)控。

結(jié)論：

我們證明了tRF-Leu可以通過靶向BIRC5抑制乳腺癌的化療耐藥。這些發(fā)現(xiàn)可能會發(fā)現(xiàn)新的乳腺癌治療生物標(biāo)志物，并為逆轉(zhuǎn)化療耐藥帶來新的策略。

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