Ferroptosis is involved in the progression of hepatocellular carcinoma through the circ0097009/miR-1261/SLC7A11 axis.

Ferroptosis is involved in the progression of hepatocellular carcinoma through the circ0097009/miR-1261/SLC7A11 axis.
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铁死亡通过circ0097009/miR-1261/SLC7A11轴参与肝细胞癌的进展

DOI:
10.21037/atm-21-997
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发表时间:
2021-04
影响因子:
--
通讯作者:
Zhao M
Zhao M
中科院分区:
医学4区
文献类型:
--
作者:
Lyu N;Zeng Y;Kong Y;Chen Q;Deng H;Ou S;Bai Y;Tang H;Wang X;Zhao M

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环状RNA(CircRNA)是一类非编码RNA,在肿瘤发生中起重要作用。然而,circRNA如何调节肝细胞癌(HCC)的进展仍不清楚。在本研究中,对HCC组织进行circRNA微阵列分析以鉴定差异表达的circRNA。对HCC细胞系和组织进行定量逆转录聚合酶链反应(qRT-PCR)分析,发现circ 0097009显著上调。通过一系列实验研究了circ 0097009在HCC中的功能,包括细胞增殖、侵袭和小鼠异种移植试验。此外,荧光素酶测定和RNA免疫沉淀(RIP)测定用于探索HCC中circ 0097009、microRNA-1261(miR-1261)和溶质载体家族7成员11(SLC 7A 11)的相互作用。微阵列分析和qRT-PCR验证了circRNA,circ 0097009,在HCC组织和细胞系中显著上调。circ 0097009基因的敲除抑制了肝癌细胞的增殖和侵袭。荧光素酶报告基因分析显示,circ 0097009和SLC 7A 11直接与miR-1261结合。随后的实验表明,circ 0097009和SLC 7A 11通过circ 0097009对miR-1261的海绵作用来调节其表达。Circ 0097009作为竞争性内源性RNA通过海绵状吸收HCC中的miR-1261来调节癌细胞铁凋亡的关键调节因子SLC 7A 11的表达。Circ 0097009可用作HCC的诊断生物标志物和HCC治疗的潜在靶点。
Circular RNAs (circRNAs) are a class of non-coding RNAs that have been demonstrated to play important roles in tumorigenesis. However, how circRNAs regulate the progression of hepatocellular cancer (HCC) remains unclear. In the present study, circRNA microarray analyses were performed with HCC tissues to identify circRNAs that are differentially expressed. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was conducted on HCC cell lines and tissues, and circ0097009 was found to be significantly upregulated. The functions of circ0097009 in HCC were investigated by a series of experiments, including cell proliferation, invasion, and mouse xenograft assays. Additionally, luciferase assays and RNA immunoprecipitation (RIP) assays were used to explore the interactions of circ0097009, microRNA-1261 (miR-1261), and solute carrier family 7 member 11 (SLC7A11) in HCC. Microarray analysis and qRT-PCR verified that circRNA, circ0097009, was significantly upregulated in HCC tissues and cell lines. Knockdown of circ0097009 inhibited the proliferation and invasion of HCC cells. Luciferase reporter assays showed that circ0097009 and SLC7A11 directly bound to miR-1261. Subsequent experiments showed that circ0097009 and SLC7A11 reciprocally regulated their expression via miR-1261 sponging by circ0097009. Circ0097009 acts as a competing endogenous RNA to regulate the expression of SLC7A11, a key regulator of cancer cell ferroptosis, by sponging miR-1261 in HCC. Circ0097009 may be used as a diagnostic biomarker for HCC and as a potential target for HCC therapy.
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