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环状RNA La相关RNA结合蛋白4与肿瘤分期降低以及更好的预后相关,并促进乳腺癌对阿霉素的化疗敏感性。

Circular RNA La-related RNA-binding protein 4 correlates with reduced tumor stage, as well as better prognosis, and promotes chemosensitivity to doxorubicin in breast cancer.

作者信息

Zhang Xiaoyi, Su Xinyu, Guo Zhe, Jiang Xueqing, Li Xun

机构信息

Department of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

J Clin Lab Anal. 2020 Jul;34(7):e23272. doi: 10.1002/jcla.23272. Epub 2020 Mar 18.

Abstract

OBJECTIVE

We aimed to evaluate the correlation of circular RNA La-related RNA-binding protein 4 (circ-LARP4) with tumor characteristics and prognosis, and its effect on chemosensitivity in breast cancer.

METHODS

Circ-LARP4 from tumor and adjacent tissues of 283 female breast cancer patients underwent resection was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Tumor features, disease-free survival (DFS), and overall survival (OS) were recorded. In vitro, circ-LARP4 in human normal mammary epithelial cells (HMEC) and breast cancer cell lines was detected by RT-qPCR. MCF-7 and MDA-MB-231 cells were transfected with circ-LARP4 overexpression plasmid (as OE-Circ group) and control overexpression plasmid (as OE-Control group). Relative cell viability under different concentrations of doxorubicin was measured.

RESULTS

Circ-LARP4 was decreased in tumor tissues than adjacent tissues (P < .001). Tumor circ-LARP4 negatively correlated with tumor size (P = .001), T stage (P = .009), N stage (P = .006), and TNM stage (P < .001), whereas positively correlated with DFS (P = .004) and OS (P < .001). In vitro, circ-LARP4 was decreased MCF-7, BT474, MDA-MB-231, and MDA-MB-468 cell lines than HMEC (all P < .001). Relatively cell viability of MCF-7 cells (at 20 nmol/L [P < .05], 40 nmol/L [P < .01], 80 nmol/L [P < .05] of doxorubicin) and MDA-MB-231 cells (at 120 nmol/L [P < .05], 240 nmol/L [P < .05] of doxorubicin) was decreased in OE-Circ group than OE-Control group. IC value of doxorubicin was decreased in OE-Circ group than OE-Control group in MCF-7 and MDA-MB-231 cell lines (both P < .01).

CONCLUSION

Circ-LARP4 was a potential prognostic biomarker, which might improve the management of breast cancer.

摘要

目的

我们旨在评估环状RNA拉相关RNA结合蛋白4(circ-LARP4)与肿瘤特征及预后的相关性,及其对乳腺癌化疗敏感性的影响。

方法

采用逆转录定量聚合酶链反应(RT-qPCR)检测283例接受手术切除的女性乳腺癌患者肿瘤组织及癌旁组织中的circ-LARP4。记录肿瘤特征、无病生存期(DFS)和总生存期(OS)。体外实验中,通过RT-qPCR检测人正常乳腺上皮细胞(HMEC)和乳腺癌细胞系中的circ-LARP4。用circ-LARP4过表达质粒(作为OE-Circ组)和对照过表达质粒(作为OE-Control组)转染MCF-7和MDA-MB-231细胞。测量不同浓度阿霉素作用下的相对细胞活力。

结果

肿瘤组织中的circ-LARP4低于癌旁组织(P <.001)。肿瘤circ-LARP4与肿瘤大小(P =.001)、T分期(P =.009)、N分期(P =.006)和TNM分期(P <.001)呈负相关,而与DFS(P =.004)和OS(P <.001)呈正相关。体外实验中,MCF-7、BT474、MDA-MB-231和MDA-MB-468细胞系中的circ-LARP4低于HMEC(均P <.001)。与OE-Control组相比,OE-Circ组中MCF-7细胞(阿霉素浓度为20 nmol/L时[P <.05]、40 nmol/L时[P <.01]、80 nmol/L时[P <.05])和MDA-MB-231细胞(阿霉素浓度为120 nmol/L时[P <.05]、240 nmol/L时[P <.05])的相对细胞活力降低。在MCF-7和MDA-MB-231细胞系中,与OE-Control组相比,OE-Circ组中阿霉素的半数抑制浓度(IC)值降低(均P <.01)。

结论

Circ-LARP4是一种潜在的预后生物标志物,可能改善乳腺癌的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d35/7370746/8c2dcf83588d/JCLA-34-e23272-g001.jpg

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