Hypoxia-induced circRNF13 promotes the progression and glycolysis of pancreatic cancer.
Hypoxia-induced circRNF13 promotes the progression and glycolysis of pancreatic cancer.
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缺氧诱导的circRNF13促进胰腺癌的进展和糖酵解
DOI：
10.1038/s12276-022-00877-y
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发表时间：
2022-11
影响因子：
12.8
通讯作者：
Wan, Rong
中科院分区：
文献类型：
--
作者：
Zhao, Qiuyan;Zhu, Zhonglin;Xiao, Wenqin;Zong, Guanzhao;Wang, Chuanyang;Jiang, Weiliang;Li, Kai;Shen, Jie;Guo, Xingya;Cui, Jianhua;Guo, Lihong;Wan, Rong
胰腺癌（Pancreatic cancer，PC）是最常见的恶性肿瘤之一。快速进展和远处转移是患者死亡的主要原因。缺氧是多种癌症的标志，并参与肿瘤生物学。然而，关于circRNA在糖酵解和缺氧介导的PC进展中的作用知之甚少。在这里，缺氧相关的circRNA的表达模式进行了分析，使用RNA测序。一个独特的circRNA称为circRNF 13被发现在PC组织中上调，可能是一个潜在的预后指标。HIF-1α和EIF 4A 3参与调节circRNF 13的生物合成。此外，证实circRNF 13对细胞增殖、血管生成、侵袭和糖酵解发挥刺激作用。重要的是，我们发现circRNF 13通过充当miR-654- 3 p海绵来促进PDK 3水平，从而促进PC恶性过程。总之，我们的研究结果表明，由HIF-1α和EIF 4A 3介导的缺氧诱导的circRNF 13促进PC中的肿瘤进展和糖酵解，表明circRNF 13作为PC的预后生物标志物和治疗靶点的潜力。胰腺肿瘤内的低氧（缺氧）条件促进了新鉴定的与侵袭性肿瘤生长相关的环状RNA分子的产生。胰腺癌通常难以治疗，并且已知肿瘤内部的缺氧条件有助于对化疗产生更大的抗性。几项研究表明，这些条件也会导致某些环状RNA的产生增加，中国上海交通大学医学院的Rong Wan领导的研究人员着手鉴定缺氧胰腺肿瘤组织中产生的特定RNA分子。活检样本中含有高水平的一种这样的RNA，circRNF 13，一直与预后不良有关。研究人员还确定了由circRNF 13调节的下游靶标，这些靶标有助于疾病进展，这可能为药物开发提供新的靶标。
Pancreatic cancer (PC) is one of the most malignant tumors. Rapid progression and distant metastasis are the main causes of patient death. Hypoxia is a hallmark of multiple cancers and is involved in tumor biology. However, little is known about the roles of circRNAs in glycolysis and hypoxia-mediated progression of PC. Here, the expression pattern of hypoxia-related circRNAs was analyzed using RNA sequencing. A unique circRNA termed circRNF13 was found to be upregulated in PC tissues and may be a potential prognostic indicator. HIF-1α and EIF4A3 are involved in regulating the biogenesis of circRNF13. Furthermore, circRNF13 was validated to exert a stimulative effect on cell proliferation, angiogenesis, invasion and glycolysis. Importantly, we found that circRNF13 promoted PDK3 levels by acting as a miR-654-3p sponge, thus promoting the PC malignant process. Collectively, our results reveal that hypoxia-induced circRNF13 mediated by HIF-1α and EIF4A3 promotes tumor progression and glycolysis in PC, indicating the potential of circRNF13 as a prognostic biomarker and therapeutic target for PC. The low-oxygen (hypoxic) conditions within pancreatic tumors promote production of a newly identified circular RNA molecule associated with aggressive tumor growth. Pancreatic cancers are generally difficult to treat, and the hypoxic conditions of the tumor interior are known to contribute to greater resistance to chemotherapy. Several studies have indicated that these conditions also lead to greater production of certain circular RNAs, and researchers led by Rong Wan at Shanghai Jiao Tong University School of Medicine, China, set out to identify specific RNA molecules produced within hypoxic pancreatic tumor tissue. Biopsy samples containing high levels of one such RNA, circRNF13, were consistently linked with a poor prognosis. The researchers also identified downstream targets modulated by circRNF13 that contribute to progression, which could offer new targets for drug development.
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