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Circ-TFF1 Facilitates Breast Cancer Development via Regulation of miR-338-3p/FGFR1 Axis
Biochemical Genetics ( IF 2.4 ) Pub Date : 2021-07-04 , DOI: 10.1007/s10528-021-10102-6
Long Wan 1 , Qi Han 2 , Bisheng Zhu 2 , Zhihua Kong 1 , Enrong Feng 3
Affiliation  

Some circular RNAs (circRNAs) have been verified to act as essential regulators in the progression of breast cancer (BC). We aimed to investigate the role of circRNA trefoil factor 1 (circ-TFF1) in BC progression. The expression of circ-TFF1, microRNA-338-3p (miR-338-3p) and fibroblast growth factor receptor 1 (FGFR1) mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was evaluated by methylthiazolyldiphenyl-tetrazolium bromide (MTT), colony formation, and 5-Ethynyl-2′-deoxyuridine (EDU) assays. Cell apoptosis and invasion were assessed by flow cytometry and transwell assay, respectively. Cellular glycolysis, including glucose consumption, lactate production, and ATP/ADP ratio, was detected by commercial kits. All protein levels were measured by western blot assay. The relationship between miR-338-3p and circ-TFF1 or FGFR1 was predicted by online bioinformatics tool and verified by dual-luciferase reporter assay. Xenograft tumor model was established to verify the function of circ-TFF1 in vivo. Circ-TFF1 was overexpressed in BC tissues and cells. Circ-TFF1 knockdown inhibited cell proliferation, invasion and glycolysis and induced apoptosis in BC cells. Circ-TFF1 acted as a sponge of miR-338-3p, and the effects of circ-TFF1 knockdown on BC cell proliferation, apoptosis, invasion, and glycolysis were abolished by miR-338-3p inhibition. FGFR1 was confirmed to be a target gene of miR-338-3p, and miR-338-3p played a tumor-suppressive role in BC by targeting FGFR1. Moreover, circ-TFF1 regulated FGFR1 expression by targeting miR-338-3p. Additionally, circ-TFF1 knockdown hampered tumorigenesis in vivo. Circ-TFF1 knockdown suppressed BC progression by regulating miR-338-3p/FGFR1 axis, providing a promising therapeutic target for BC.



中文翻译:

Circ-TFF1 通过调节 miR-338-3p/FGFR1 轴促进乳腺癌的发展

一些环状 RNA (circRNA) 已被证实可作为乳腺癌 (BC) 进展的重要调节因子。我们旨在研究 circRNA 三叶因子 1 (circ-TFF1) 在 BC 进展中的作用。通过定量实时聚合酶链反应 (qRT-PCR) 测量 circ-TFF1、microRNA-338-3p (miR-338-3p) 和成纤维细胞生长因子受体 1 (FGFR1) mRNA 的表达。通过甲基噻唑基二苯基溴化四唑 (MTT)、集落形成和 5-Ethynyl-2'-脱氧尿苷 (EDU) 测定法评估细胞增殖。细胞凋亡和侵袭分别通过流式细胞术和 transwell 测定法进行评估。通过商业试剂盒检测细胞糖酵解,包括葡萄糖消耗、乳酸产生和 ATP/ADP 比率。通过蛋白质印迹测定测量所有蛋白质水平。通过在线生物信息学工具预测miR-338-3p与circ-TFF1或FGFR1之间的关系,并通过双荧光素酶报告基因分析验证。建立异种移植肿瘤模型以验证circ-TFF1在体内的功能。Circ-TFF1 在 BC 组织和细胞中过表达。Circ-TFF1 敲低抑制细胞增殖、侵袭和糖酵解,并诱导 BC 细胞凋亡。Circ-TFF1 充当 miR-338-3p 的海绵,并且 circ-TFF1 敲低对 BC 细胞增殖、凋亡、侵袭和糖酵解的影响被 miR-338-3p 抑制所消除。FGFR1被证实是miR-338-3p的靶基因,miR-338-3p通过靶向FGFR1在BC中发挥抑癌作用。此外,circ-TFF1 通过靶向 miR-338-3p 调节 FGFR1 的表达。此外,circ-TFF1 敲低阻碍了肿瘤发生 建立异种移植肿瘤模型以验证circ-TFF1在体内的功能。Circ-TFF1 在 BC 组织和细胞中过表达。Circ-TFF1 敲低抑制细胞增殖、侵袭和糖酵解,并诱导 BC 细胞凋亡。Circ-TFF1 充当 miR-338-3p 的海绵,并且 circ-TFF1 敲低对 BC 细胞增殖、凋亡、侵袭和糖酵解的影响被 miR-338-3p 抑制所消除。FGFR1被证实是miR-338-3p的靶基因,miR-338-3p通过靶向FGFR1在BC中发挥抑癌作用。此外,circ-TFF1 通过靶向 miR-338-3p 调节 FGFR1 的表达。此外,circ-TFF1 敲低阻碍了肿瘤发生 建立异种移植肿瘤模型以验证circ-TFF1在体内的功能。Circ-TFF1 在 BC 组织和细胞中过表达。Circ-TFF1 敲低抑制细胞增殖、侵袭和糖酵解,并诱导 BC 细胞凋亡。Circ-TFF1 充当 miR-338-3p 的海绵,并且 circ-TFF1 敲低对 BC 细胞增殖、凋亡、侵袭和糖酵解的影响被 miR-338-3p 抑制所消除。FGFR1被证实是miR-338-3p的靶基因,miR-338-3p通过靶向FGFR1在BC中发挥抑癌作用。此外,circ-TFF1 通过靶向 miR-338-3p 调节 FGFR1 的表达。此外,circ-TFF1 敲低阻碍了肿瘤发生 侵袭和糖酵解并诱导 BC 细胞凋亡。Circ-TFF1 充当 miR-338-3p 的海绵,并且 circ-TFF1 敲低对 BC 细胞增殖、凋亡、侵袭和糖酵解的影响被 miR-338-3p 抑制所消除。FGFR1被证实是miR-338-3p的靶基因,miR-338-3p通过靶向FGFR1在BC中发挥抑癌作用。此外,circ-TFF1 通过靶向 miR-338-3p 调节 FGFR1 的表达。此外,circ-TFF1 敲低阻碍了肿瘤发生 侵袭和糖酵解并诱导 BC 细胞凋亡。Circ-TFF1 充当 miR-338-3p 的海绵,并且 circ-TFF1 敲低对 BC 细胞增殖、凋亡、侵袭和糖酵解的影响被 miR-338-3p 抑制所消除。FGFR1被证实是miR-338-3p的靶基因,miR-338-3p通过靶向FGFR1在BC中发挥抑癌作用。此外,circ-TFF1 通过靶向 miR-338-3p 调节 FGFR1 的表达。此外,circ-TFF1 敲低阻碍了肿瘤发生 circ-TFF1 通过靶向 miR-338-3p 调节 FGFR1 的表达。此外,circ-TFF1 敲低阻碍了肿瘤发生 circ-TFF1 通过靶向 miR-338-3p 调节 FGFR1 的表达。此外,circ-TFF1 敲低阻碍了肿瘤发生活体。Circ-TFF1 敲低通过调节 miR-338-3p/FGFR1 轴抑制 BC 进展,为 BC 提供有希望的治疗靶点。

更新日期:2021-07-04
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