自噬研究不得不了解的分子通路及数据库
2016年的诺贝尔生理学或医学奖颁发给了日本科学家大隅良典，以奖励他在阐明细胞自噬的分子机制和生理功能上的开拓性研究。此次的诺奖颁布又引发了我们对自噬研究期望，尤其是2017年的国科金，相信不少小伙伴都跃跃欲试想沾一下诺贝奖的光。
自噬，对大家来说都不陌生。之前小张也给大家讲过：关于国科金写作选择自噬的N种可能性（点我进行查看，或者点我也行）。如果你想做自噬而又缺少一些思路，说不定可以从分子及通路上面着手。那么今天给大家理一下自噬过程中的相关参与调控的分子通路，以及若干自噬相关的数据库。
在开始前，先强行科普一下自噬是什么？很多心知肚明的小伙伴可自行跳过哦。
自噬，就是细胞降解回收自己零部件的过程；这个过程能快速提供能量和材料用于应急；还能用来对抗病原体、清除受损结构。
其次，自噬与细胞凋亡的关系？相信很多人都思考过。
凋亡是正常的细胞死亡途径，凋亡后，细胞必定死亡；自噬只是细胞在高胁迫的环境中的一种应急机制，旨在为自身提供营养或者降解掉错误折叠蛋白等，不一定引起死亡。
自噬发生的过程？
细胞质中的线粒体等细胞器首先被称为“隔离膜”的囊泡所包被,这种“隔离膜”主要来自于内质网和高尔基体;囊泡最终形成双层膜结构,即自吞噬体;自吞噬体与胞内体融合形成中间自体吞噬泡;最终自体吞噬泡的外膜与溶酶体融合形成降解自体吞噬泡,由溶酶体内的酶降解自体吞噬泡中的内容物和内膜。
自噬发生过程中最关键的是自噬体的形成，其大小约为 500 nm左右，囊泡内常见的包含物有胞质成分和某些细胞器如线粒体、内吞体、过氧化物酶体等。与其他细胞器相比，自噬体的半衰期很短，只有 8 min 左右，说明自噬是细胞对于环境变化的有效反应。
自噬有哪些通路及分子参与：
在吞噬泡诱导过程中miRNA靶向的自噬相关通路
| Pathway | Target | Autophagy | miRNA |
| Hypoxia | NDRG2 | activated | MIR301A/B |
| PI3K-AKT-MTOR | TGFBR2 | inhibited | MIR19A/B-3p |
| IGF1R | activated | MIRLET7I/MIR100 | |
| PTEN | activated | MIR21 | |
| MIR21 | inhibited | MIR451 | |
| RHEB | activated | MIR155 | |
| RICTOR | activated | MIR155/MIR15A/MIR16 | |
| RPS6KB2 | activated | MIR155 | |
| Ca2+-AMPK-MTOR | IP3K2 | activated | Drosophila/mir-14 |
| TRPM3 | inhibited | MIR204 | |
| TP53 | TIGAR | activated | MIR144 |
| CDKN1A | activated | MIR182 | |
| DRAM1 | inhibited | MIR199A-5p | |
| SIRT1 | inhibited | MIR140-3p/MIR212/MIR34A | |
| HMGB1 | inhibited | MIR129-5p/-141/-218/LET7F/-22 | |
| MAPK1/ERK2-MAPK3/ERK1 | DUSP4/5 | activated | MIR26A |
| Translational factors | FOXO3 | inhibited | MIR182/MIR212/132 |
| TFAP2A | inhibited | MIR638 | |
| STAT3 | inhibited | MIR17-5p | |
| Mitophagy | BNIP3L | inhibited | MIR137 |
| FUNDC1 | inhibited | MIR137 | |
| UCP2 | inhibited | MIR214 | |
| CDKN1B -CDK2-MTOR | CDKN1B | inhibited | MIR221 |
| Hedgehog | Gas1 | activated | MIR148A |
| Others | PSME4 | inhibited | MIR29B |
| ARC | activated | MIR325 | |
| UBQLN1 | inhibited | MIR200C |
自噬过程中lncRNAs靶向特定的靶基因及机制
| Name | Disease phenotype | Regulation | Mechanism |
| APF | myocardial infarction | upregulate | Binds MIR188-3p to affect ATG7 expression |
| TGFB2-OT1 | inflammation | _ | Binds MIR3960, MIR4488 and MIR4459 to target ATG13, CERS1, NAT8L and LARP1 |
| PTENP1 | hepatocellular carcinoma | downregulate | Represses oncogenic PI3K-AKT signaling pathway and elicit autophagy via sequestering MIR17, MIR19B and MIR20A in vitro |
| NBR2 | human cancers | downregulate | Induced by the STK11-AMPK pathway under energy stress and interacts with AMPK to promotes kinase activity in turn |
| PVT1 | diabetes | upregulate | unknown |
| MEG3 | mycobacterial infection bladder cancer | downregulate | Linked to MTOR activity and PI3K-AKT signaling pathway to regulate autophagy |
| PCGEM1 | osteoarthritis | upregulate | Increases the expression of ATG12, ATG5, ATG3 and BECN1 |
| BANCR | papillary thyroid carcinoma | upregulate | unknown |
| GAS5 | Osteoarthritis non-small cell lung cancer | upregulate | Acts as a negative regulator of MIR21 in autophagy |
| Chast | cardiovascular | downregulate | Impedes Plekhm1 to autophagy inhibition and cardiomyocyte hypertrophy |
| H19 | diabetic cardiomyopathy | downregulate | Regulates DIRAS3 expression and promote MTOR phosphorylation to inhibit autophagy as cardiomyocytes exposed to high glucose |
| loc146880 | lung cancer | upregulate | PM2.5 exposure induces ROS, which activates loc146880 expression, and the lncRNA upregulates autophagy in return |
| HOTAIRM1 | myeloid differentiation | upregulate | Acts as a miRNA sponge in a pathway that included MIR20A, MIR106B, MIR125B and their targets ULK1, E2F1 and DRAM2. |
| AlncRNA | hepatocellular carcinoma | upregulate | Targets multiple miRNAs including MIR21, MIR153, MIR216A, MIR217, MIR494 and MIR10A-5p |
| MALAT1 | hepatocellular carcinoma aggressive pancreatic cancer | upregulate | EPAS1/HIF-2α-MALAT1-MIR216B axis regulating MDR of HCC cells via modulating autophagy in hepatocellular carcinoma and via HuR-TIA-1-mediated autophagy activation in aggressive pancreatic cancer |
| AK156230 | mouse embryonic fibroblasts | upregulate | unknown |
| HOTAIR | hepatocellular carcinoma | upregulate | Activates autophagy by increasing ATG3 and ATG7 expression |
| HNF1A-AS1 | hepatocellular carcinoma | upregulate | Acts as an oncogene in tumor growth and apoptosis through sponging tumor-suppressive MIR30B-5p (MIR30B) and derepress BCL2 |
非编码RNA相关的自噬数据库
Database Name | Website |
Autophagy Regulatory Network | http://autophagy-regulation.org/search |
The Autophagy Database | http://www.tanpaku.org/autophagy/index.html |
ncRDeathDB | http://www.rna-society.org/ncrdeathdb/index.php |
GAMDB | http://gamdb.liu-lab.com/index.php |
相关文章：
Long noncoding RNA Chast promotes cardiac remodeling.
Suppression of hepatocellular carcinoma by baculovirus-mediated expression of long non-coding RNA PTENP1 and MicroRNA regulation.
APF lncRNA regulates autophagy and myocardial infarction by targeting miR-188-3p.
PCGEM1 stimulates proliferation of osteoarthritic synoviocytes by acting as a sponge for miR-770.
A long non-coding RNA, GAS5, plays a critical role in the regulation of miR-21 during osteoarthritis.
LncRNA H19 inhibits autophagy by epigenetically silencing of DIRAS3 in diabetic cardiomyopathy.
相关基金：
破骨细胞自噬在糖皮质激素诱导的骨丢失过程中的作用及PI3K/Akt/mTOR信号通路的调节机制
自噬抑制剂通过调控PTEN-PI3K/AKT/mTOR信号通路逆转胃肠道间质瘤
伊马替尼耐药的实验研究 Ca-A/K通道在新生大鼠缺氧缺血海马锥体神经元自噬性死亡中的作用及机制
内质网应激-mTOR-自噬通路介导硫化氢心脏保护作用及机制
文章导读：
参考文献：
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2. The Emergence of Noncoding RNAs as Heracles in Autophagy.Autophagy. 2017 Apr 25:0. doi: 10.1080/15548627.
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