Dysregulation of the circ_0087502/miR-1179/TGFBR2 pathway supports gemcitabine resistance in pancreatic cancer.

IF 4.4 4区医学 Q2 ONCOLOGY

Cancer Biology & Therapy Pub Date : 2023-12-31 Epub Date: 2023-10-16 DOI:10.1080/15384047.2023.2258566

Mingliu Chen, Xinxiu Liu, Jinpeng Lu, Haiwen Teng, Chengui Yu, Yingchun Liu, Yansong Zheng

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Abstract

Background: Circular RNAs (circRNAs) are a cohort of non-coding RNAs generated by back-splicing events. Accumulating evidence supports the crucial role of circRNAs in human tumorigenesis, metastasis, and chemoresistance. However, the role and mechanism of circRNA circ_0087502 in pancreatic cancer are yet unknown.

Methods: The expression and function of circ_0087502 in pancreatic cancer were investigated using qRT-PCR and cell experiments. The predicted binding between circ_0087502 and microRNA-1179 (miR-1179), and between miR-1179 and TGFBR2, were examined using reporter assays.

Results: Pancreatic cancer tissues and cell lines were discovered to express circ_0087502 at higher levels. Patients with pancreatic cancer who express circ_0087502 at high levels have a worse prognosis. In addition, circ_0087502 knockdown reduced the proliferation, migration, and invasion of pancreatic cancer cells and made them more sensitive to gemcitabine treatment. We found that circ_0087502 worked as a sponge for miR-1179, allowing miR-1179 to bind to the critical oncogene TGFBR2 in its 3'-untranslated region (3'-UTR). Pancreatic cancer cells were highly resistant to gemcitabine and had increased proliferation, migration, and invasion when miR-1179 was inhibited or overexpressed.

Conclusion: These results confirm that circ_0087502 activates the miR-1179/TGFBR2 axis to promote gemcitabine resistance in pancreatic cancer. Thus, our data might lay the groundwork for developing novel therapeutic strategies targeting circ_0087502 in pancreatic cancer patients.

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circ_0087502/miR-1179/TGFBR2通路的失调支持胰腺癌症中的吉西他滨耐药性。

背景：环状RNA（circRNAs）是一组由反剪接事件产生的非编码RNA。越来越多的证据支持circRNAs在人类肿瘤发生、转移和化疗耐药性中的关键作用。然而，circRNAcirc_0087502在癌症中的作用和机制尚不清楚。方法：采用qRT-PCR和细胞实验方法研究circ_0087502在癌症组织中的表达及功能。使用报告基因分析检测circ_0087502和微小RNA-1179（miR-1179）之间以及miR-1179和TGFBR2之间的预测结合。结果：发现癌症胰腺组织和细胞系在较高水平上表达circ_0087502。高水平表达circ_0087502的癌症胰腺癌患者预后较差。此外，circ_0087502敲低降低了胰腺癌症细胞的增殖、迁移和侵袭，使其对吉西他滨治疗更敏感。我们发现circ_0087502作为miR-1179的海绵，使miR-1179能够在其3'-非翻译区（3'-UTR）与关键癌基因TGFBR2结合。当miR-1179被抑制或过表达时，胰腺癌症细胞对吉西他滨具有高度耐药性，并具有增加的增殖、迁移和侵袭。结论：这些结果证实circ_0087502激活miR-1179/TGFBR2轴以促进癌症对吉西他滨的耐药性。因此，我们的数据可能为开发针对癌症患者的circ_0087502的新治疗策略奠定基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Biology & Therapy 医学-肿瘤学

CiteScore

7.00

自引率

0.00%

发文量

审稿时长

2.3 months

期刊介绍： Cancer, the second leading cause of death, is a heterogenous group of over 100 diseases. Cancer is characterized by disordered and deregulated cellular and stromal proliferation accompanied by reduced cell death with the ability to survive under stresses of nutrient and growth factor deprivation, hypoxia, and loss of cell-to-cell contacts. At the molecular level, cancer is a genetic disease that develops due to the accumulation of mutations over time in somatic cells. The phenotype includes genomic instability and chromosomal aneuploidy that allows for acceleration of genetic change. Malignant transformation and tumor progression of any cell requires immortalization, loss of checkpoint control, deregulation of growth, and survival. A tremendous amount has been learned about the numerous cellular and molecular genetic changes and the host-tumor interactions that accompany tumor development and progression. It is the goal of the field of Molecular Oncology to use this knowledge to understand cancer pathogenesis and drug action, as well as to develop more effective diagnostic and therapeutic strategies for cancer. This includes preventative strategies as well as approaches to treat metastases. With the availability of the human genome sequence and genomic and proteomic approaches, a wealth of tools and resources are generating even more information. The challenge will be to make biological sense out of the information, to develop appropriate models and hypotheses and to translate information for the clinicians and the benefit of their patients. Cancer Biology & Therapy aims to publish original research on the molecular basis of cancer, including articles with translational relevance to diagnosis or therapy. We will include timely reviews covering the broad scope of the journal. The journal will also publish op-ed pieces and meeting reports of interest. The goal is to foster communication and rapid exchange of information through timely publication of important results using traditional as well as electronic formats. The journal and the outstanding Editorial Board will strive to maintain the highest standards for excellence in all activities to generate a valuable resource.