2019年诺贝尔生理学与医学奖授予哈佛医学院达纳-法伯癌症研究所的威廉·凯林（ William G. Kaelin, Jr.），牛津大学和弗朗西斯·克里克研究所的彼得·拉特克利夫（ Peter J. Ratcliffe） 以及美国约翰霍普金斯大学医学院的格雷格·塞门扎（Gregg L. Semenza），以表彰他们发现和解析氧感知信号通路的工作。
图1 2019年诺贝尔生理医学奖获得（图片来自诺贝尔奖官方网站）
今年获奖的这个信号通路可以用下图概括：在正常氧浓度条件下（Normoxia），氧气可促进HIF-1α的羟基化，随后被VHL识别并介导多聚泛素化随后被蛋白酶体降解。但低氧条件时（Hypoxia），HIF-1α的羟基化程度减弱，因而得以保留，HIF-1α转移入核，与ARNT结合到靶基因启动子区的HRE元件，调控下游基因的转录表达。
图2 氧感知信号通路 （图片来自诺贝尔奖官方网站）
已发表的文章也有关于HIF-1α通路和Hypoxia条件相关的circRNA研究报道，本文将这一通路相关的研究论文做了汇总整理，希望能给大家提供帮助。
表1 已发表氧感知通路相关的circRNA文章汇总
| 编号 | 论文题目 | 杂志 | 发表时间 | 主要内容 |
| 1 | Circular RNA circPIP5K1A promotes non-small cell lung cancer proliferation and metastasis through miR-600/HIF-1α regulation | J Cell Biochem. | 2019 Nov | 非小细胞肺癌中circ PIP5K1A 通过miR-600/ HIF-1α 调控细胞增殖和迁移 |
| 2 | lncRNA/circRNA‑miRNA‑mRNA ceRNA network in lumbar intervertebral disc degeneration | Mol Med Rep. | 2019 Oct | 椎间盘退变中非编码RNA调控网络分析，PPI通路分析表明 HIF等信号通路起重要作用 |
| 3 | Circular RNA MAT2B Promotes Glycolysis and Malignancy of Hepatocellular Carcinoma Through the miR-338-3p/PKM2 Axis Under Hypoxic Stress | Hepatology | 2019 Oct | 低氧条件下circMTA2B通过miR-338-3p/PKM2促进肝癌细胞糖酵解和迁移 |
| 4 | A combined computational pipeline to detect circular RNAs in human cancer cells under hypoxic stress | J Mol Cell Biol. | 2019 Sep 27 | 肿瘤细胞低氧条件circRNA表达谱系统分析的流水线体系 |
| 5 | Knockdown of circDENND4C inhibits glycolysis, migration and invasion by up-regulating miR-200b/c in breast cancer under hypoxia | J Exp Clin Cancer Res. | 2019 Sep 5 | 乳腺癌细胞低氧条件下敲低circDENND4C的机制研究 |
| 6 | Circular RNA Expression Profiling and Selection of Key Circular RNAs in the Hypothalamus of Heat-Acclimated Rats | Front Physiol. | 2019 Aug 28 | 热适应大鼠下丘脑circRNA表达谱研究。其中通路富集结果中包含rno_circRNA_014301-vs-rno-miR-3575-vs-Hif-1α通路。 |
| 7 | Knockdown of cZNF292 suppressed hypoxic human hepatoma SMMC7721 cell proliferation, vasculogenic mimicry, and radioresistance | Cell Signal | 2019 Aug | 敲降cZNF292抑制低氧条件下肝癌细胞SMMC7721增殖，血管生成和辐射耐受 |
| 8 | A Noncoding Regulatory RNAs Network Driven by Circ-CDYL Acts Specifically in the Early Stages Hepatocellular Carcinoma | Hepatology | 2019 May 30 | Circ-CDYL在早期肝癌中调控网络研究，其中包括对HIF-1AN的调控作用 |
| 9 | Circular RNA CDR1as acts as a sponge of miR-135b-5p to suppress ovarian cancer progression | Onco Targets Ther. | 2019 May 17 | CDR1as通过竞争性结合miR-135b-5p调控HIF-1AN（HIF-1α 抑制因子） |
| 10 | Circular RNA circPTK2 regulates oxygen-glucose deprivation-activated microglia-induced hippocampal neuronal apoptosis via miR-29b-SOCS-1-JAK2/STAT3-IL-1β signaling | Int J Biol Macromol. | 2019 May 15 | circPTK2通过miR-29b-SOCS-1-JAK2 /STAT3-IL-1β通路调控氧葡萄糖剥夺激活的小胶质细胞诱导的海马神经元凋亡 |
| 11 | Circular RNA Ttc3 regulates cardiac function after myocardial infarction by sponging miR-15b | J Mol Cell Cardiol. | 2019 May | 缺血性心肌和缺氧损伤的心肌细胞circ-Ttc3 显著升高，circ-Ttc3通过吸附miR-15b促进Arl2表达，抵消缺氧诱导的ATP耗竭和凋亡 |
| 12 | Hypoxia-associated circDENND2A promotes glioma aggressiveness by sponging miR-625-5p | Cell Mol Biol Lett. | 2019 Apr 2 | 低氧相关的circDENND2A通过miR-625-5p调控胶质瘤细胞侵袭 |
| 13 | Circular RNA expression profiles in neonatal rats following hypoxic-ischemic brain damage | Int J Mol Med. | 2019 Apr | 大鼠缺血缺氧后脑组织circRNA表达谱研究 |
| 14 | Altered expression of circular RNAs in human placental chorionic plate-derived mesenchymal stem cells pretreated with hypoxia | J Clin Lab Anal. | 2019 Mar | 人胎盘绒毛膜板间充质干细胞低氧刺激对circRNA表达影响 |
| 15 | Hypoxia-elevated circELP3 contributes to bladder cancer progression and cisplatin resistance | Int J Biol Sci. | 2019 Jan 1 | 膀胱癌中低氧诱导的circELP3与顺铂耐药有关 |
| 16 | Expression Profile Analysis of Circular RNAs in Ovarian Endometriosis by Microarray and Bioinformatics | Med Sci Monit. | 2018 Dec | 卵巢子宫内膜异位症circRNA表达谱研究。通路富集结果包含HIF通路 |
| 17 | A circular transcript of ncx1 gene mediates ischemic myocardial injury by targeting miR-133a-3p | Theranostics | 2018 Nov 12 | ncx1基因的circRNA通过miR-133a-3p在缺血性心肌损伤中起重要作用 |
| 18 | Characteristics of circular RNA expression in lung tissues from mice with hypoxia‑induced pulmonary hypertension | Int J Mol Med. | 2018 Sep | 低氧性肺动脉高压小鼠肺组织中环状RNA表达的特征 |
| 19 | Circular RNA Expression in the Brain of a Neonatal Rat Model of Periventricular White Matter Damage | Cell Physiol Biochem. | 2018 | 新生大鼠脑白质损伤模型circRNA表达谱分析。其中chr6: 48820833|48857932 （作者命名的circRNA）通过rno-miR-433-3p/ rno-miR-206-3p参与 HIF-1α 通路调控 |
| 20 | Whole-Transcriptome Analysis of CD133+CD144+ Cancer Stem Cells Derived from Human Laryngeal Squamous Cell Carcinoma Cells | Cell Physiol Biochem. | 2018 | 喉鳞状细胞癌干细胞转录组分析。通路分析中包括HIF通路 |
| 21 | The role of HGF-MET pathway and CCDC66 cirRNA expression in EGFR resistance and epithelial-to-mesenchymal transition of lung adenocarcinoma cells | J Hematol Oncol. | 2018 May 31 | 肺腺癌中cirRNA CCDC66在EMT中的作用 |
| 22 | Profiles of circular RNAs in human placenta and their potential roles related to preeclampsia | Biol Reprod. | 2018 May 1 | 人胎盘circRNA表达谱研究。circRNA与先兆性子痫的相关性研究。通路分析中包含了HIF通路 |
| 23 | HIF1α-associated circDENND4C Promotes Proliferation of Breast Cancer Cells in Hypoxic Environment | Anticancer Res. | 2017 Aug | 乳腺癌细胞中circDENND4C促进低氧条件下细胞增殖 |
| 24 | Circular RNA hsa_circ_0010729 regulates vascular endothelial cell proliferation and apoptosis by targeting the miR-186/HIF-1α axis | Biochem Biophys Res Commun. | 2017 Aug 19 | hsa_circ_0010729通过miR-186 /HIF-1α调节血管内皮细胞的增殖和凋亡 |
| 25 | Silencing Of Circular RNA-ZNF609 Ameliorates Vascular Endothelial Dysfunction | Theranostics | 2017 Jul 8 | 视网膜脉络丛在高糖和低氧刺激后cZNF609表达显著增高 |
| 26 | Microarray Expression Profile and Functional Analysis of Circular RNAs in Osteosarcoma | Cell Physiol Biochem. | 2017 | 骨肉瘤中circRNA表达谱研究，其中hsa_circRNA_103801可能影响HIF等通路 |
| 27 | Foxo3 circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses | Eur Heart J. | 2017 May 7 | Circ-Foxo3与HIF-1α等蛋白结合参与调控心肌衰老过程 |
| 28 | The Circular RNA Cdr1as Promotes Myocardial Infarction by Mediating the Regulation of miR-7a on Its Target Genes Expression | PLoS One | 2016 Mar 21 | 在心肌梗死面积增加的MI小鼠或缺氧治疗下的心肌细胞中，Cdr1as和miR-7a均上调 |
| 29 | Identification and Characterization of Hypoxia-Regulated Endothelial Circular RNA | Circ Res. | 2015 Oct 23 | 内皮细胞中低氧条件诱导circRNA的表达分析 |
| 30 | Cyclic RNA hsa‑circ‑000595 regulates apoptosis of aortic smooth muscle cells | Mol Med Rep. | 2015 Nov | 主动脉瘤患者的组织和低氧主动脉平滑肌细胞circRNA表达分析 |
表格的内容主要通过PubMed检索“HIF”、“Hypoxia”、“circular RNA”等关键词获得，如有遗漏的欢迎大家告知。
经过梳理，目前已发表的Hypoxia或HIF通路有关的circRNA研究论文一共30篇，早期主要在模型中进行高通量分析获得与氧感知信号通路相关的表达谱。伴随着circRNA研究的深入，与氧感知通路有关的circRNA分子机制的报道越来越多。但总体关于氧感知通路中circRNA的表达机制，circRNA调控该通路的分子机制的研究还不是非常系统和深入，包括Hypoxia条件下特异性表达的circRNA是如何“特异性”表达的，它们的生成机制是怎样的？它们的功能是怎样的？有没有特殊的功能方式？直接受HIF-1α转录调控的基因相关的circRNA有什么特征或规律？是否存在直接通过HIF-1α调控转录的circRNA分子？HIF-1α的入核和胞质中降解作用的过程是否有circRNA的参与？等等，这些基础问题有待同行们深入分析。