转自： 科研者言（微信公众号）

最近circRNA有几篇高分文章上线：

1.Circular RNA circHIPK3 modulates autophagy via MIR124-3p-STAT3-PRKAA/AMPKα signaling in STK11 mutant lung cancer.

Autophagy11.0591区. 2019 Jun 28

分子机制：circHIPK3 在其他肿瘤中有报道是促癌的作用，但是在非小细胞肺癌中没研究，作者把circHIPK3 沉默后，细胞的增殖、迁移、侵袭减弱，并且引起了大自噬，而单独转染MIR124-3p的mimics或者沉默STAT3之后，也同样能引起大自噬的发生，符合ceRNA机制的调控关系。更有趣的事情是circHIPK3 还有一个状态是线性的，我们叫做linHIPK3，而linHIPK3则有拮抗作用的调控方式，因为C:L的比例越高，肺癌细胞的大自噬程度越低，病人的预后越差，尤其是非小细胞肺癌晚期的病人。

补充：细胞自噬(autophagy)是依赖溶酶体途径对胞质蛋白和细胞器进行降解的一种过程，在进化上具有高度保守性，广泛存在于从酵母、线虫、果蝇到高等脊椎动物的细胞中。根据细胞内底物进入溶酶体腔的方式不同，细胞自噬可分为大自噬(macroautophagy)、小自噬(microautophagy)和分子伴侣介导的自噬(chaperone-mediated autophagy,CMA)三种方式。

英文摘要：The role of circular RNA in cancer is emerging. A newly reported circular RNA HIPK3 (circHIPK3) is critical in cell proliferation of various cancer types, although its role in non-small cell lung cancer (NSCLC), has yet to be elucidated. Our results provided evidence that silencing of circHIPK3 significantly impaired cell proliferation, migration, invasion and induced macroautophagy/autophagy. Mechanistically, we uncovered that autophagy was induced upon loss of circHIPK3 via the MIR124-3p-STAT3-PRKAA/AMPKa axis in STK11 mutant lung cancer cell lines (A549 and H838). STAT3 abrogation as well as transfection with a MIR124-3p mimic, recapitulated the induction of autophagy. We also demonstrated antagonistic regulation on autophagy between circHIPK3 and linear HIPK3 (linHIPK3). We therefore propose that the ratio between circHIPK3 and linHIPK3 (C:L ratio) may reflect autophagy levels in cancer cells. We observed that a high C:L ratio (>0.49) was an indicator of poor survival, especially in advanced-stage NSCLC patients. These results support that circHIPK3 is a key autophagy regulator in a subset of lung cancer and has potential clinical use as a prognostic factor. The circular RNA HIPK3 (circHIPK3) functions as an oncogene and autophagy regulator may potential use as a prognostic marker and therapeutic target in lung cancer

2. Intragenic antagonistic roles of protein and circRNA in and circRNA in tumorigenesis.

Cell Res17.8481区. 2019 Jun 17

分子机制：这里就更有意思了，研究的是同一个基因（Zbtb7a gene，also kown as POKEMON, LRF)）【2005年1月20日的《自然》杂志上刊登了一项最新研宄：Memorlal Sloan—Kettering癌症中心(MSKCC)的研宄人员最近确定出了一种新的对癌症形成至关重要的P0K红系髓性致癌因子(POK Erythrpoid Myeloid Ontogenic factor)，简称“波克曼”(POKEMON)基因】。POKEMON可以转录剪接编辑成为不同的两个转录本的故事，其可以编码成为circPOK，也可以编码成为转录因子（抑癌作用）。其中circPOK通过共激活ILF2/3复合体来促进肿瘤细胞的增殖和转移侵袭。而有趣的是，circPOK和线性的mRNA之间并没有表达量上的相关性。

英文摘要：Here we characterize a new circRNA (circPOK) encoded by the Zbtb7a gene (also kown as POKEMON, LRF) in the context of mesenchymal tumor progression. circPOK functions as a non-coding proto-oncogenic RNA independently and antithetically to its linear transcript counterpart, which acts as a tumor suppressor by encoding the Pokemon transcription factor. We find that circPOK regulates pro-proliferative and pro-angiogenic factors by co-activation of the ILF2/3 complex. Importantly, the expression of Pokemon protein and circRNA is aberrantly uncoupled in cancer through differential post-transcriptional regulation. Thus, we identify a novel type of genetic unit, the iRegulon, that yields biochemically distinct RNA products, circular and linear, with diverse and antithetical functions. Our findings further expand the cellular repertoire towards the control of normal biological outputs, while aberrant expression of such components may underlie disease pathogenesis including cancer.

3.A Noncoding Regulatory RNAs Network Driven by Circ-CDYL Acts Specifically in the Early Stages Hepatocellular Carcinoma.

Hepatology14.9711区. 2019 May 30

分子机制：该文章研究的是肝癌的，也是一个circ，叫做circ-CDYL，其在肝癌样本中高表达，增加了EPCAM阳性的肝癌细胞浸润性，分子机制上其可同时吸附miR-892a和miR-328-3p，分别促进了人肝癌衍生生长因子HDGF和缺氧诱导因子天冬酰胺羟化酶HIF1AN的表达水平，并同时激活了PI3K-AKT-mTORC1/β-catenin和NOTCH2信号通路。

英文摘要：Circ-CDYL is specifically upregulated in the early stages of HCC and therefore contributes to the properties of EPCAM-positive liver tumor-initiating cells. Circ-CDYL interacts with mRNAs encoding hepatoma-derived growth factor (HDGF) and hypoxia inducible factor asparagine hydroxylase (HIF1AN) by acts as the sponge of miR-892a and miR-328-3p, respectively. Subsequently, activation of the PI3K-AKT-mTORC1/β-catenin and NOTCH2 pathways, which promote the expression of the effect proteins baculoviral IAP repeat containing 5 (BIRC5 or SURVIVIN) and MYC proto-oncogene, is influenced by Circ-CDYL. A treatment incorporating Circ-CDYL interference and traditional enzyme inhibitors targeting PI3K and HIF1AN demonstrated highly effective inhibition of stem-like characteristics and tumor growth in HCC. Finally, we demonstrated that the Circ-CDYL expression or which combined with HDGF and HIF1AN are both independent marker for discrimination of early stages HCC with the odds ratio (OR) of 1.09 (95% CI: 1.02-1.17) and 124.58 (95% CI: 13.26-1170.56), respectively.