（一）ARID1A prevents squamous cell carcinoma initiation and chemoresistance by antagonizing pRb/E2F1/c-Myc-mediated cancer stemness
主要結(jié)論：
（1）Mechanistic studies revealed that ARID1A blocked the interaction between cyclin-dependent kinases (CDKs) and retinoblastoma protein (Rb), reducing the phosphorylation of Rb. Dephosphorylated Rb suppressed E2F1 activity and then suppressed cancer stemness by inactivating c-Myc.
（2） ARID1A depletion significantly increased the chemoresistance of SCC and that a CDK inhibitor exhibited a favorable effect on rescuing the chemoresistance caused by ARID1A loss.
![NMX_JPD)0]XX]IHG{VBZY4J.png](https://upload-images.jianshu.io/upload_images/20924877-c231911ed361b705.png?imageMogr2/auto-orient/strip%7CimageView2/2/w/1240)
主要邏輯：
ARID1A基因在腫瘤中失活突變很多期升，作者想研究它在鱗狀細(xì)胞癌中的作用。先在基因敲除小鼠模型中發(fā)現(xiàn)失活突變内列，腫瘤易發(fā)生嚎尤，這個(gè)模型算是一個(gè)亮點(diǎn)喂窟；然后在細(xì)胞系中敲掉基因拴念，發(fā)現(xiàn)促進(jìn)干性铣耘，促進(jìn)生長(zhǎng)肋殴；然后細(xì)胞RNAseq測(cè)序囤锉，發(fā)現(xiàn)敲除的細(xì)胞中，MYC相關(guān)通路最大护锤，點(diǎn)QP也驗(yàn)證ARID1A的低表達(dá)，會(huì)導(dǎo)致MYC的轉(zhuǎn)錄本和蛋白上升酿傍；既然ARID1A可以影響MYC轉(zhuǎn)錄本烙懦，是不是與調(diào)控MYC表達(dá)的轉(zhuǎn)錄因子相關(guān)，然后就在上調(diào)通路中也有E2F赤炒，它是一個(gè)轉(zhuǎn)錄因子氯析，發(fā)現(xiàn)E2F與MYC的啟動(dòng)子區(qū)域存在結(jié)合亏较；后續(xù)發(fā)現(xiàn)ARID1A影響p-Rb，E2F掩缓，證明三者有互作雪情，就做通了一個(gè)軸；后面就還涉及到上調(diào)通路中有EMT你辣，EMT與化療耐藥相關(guān)巡通，所以可能是ARID1A化療耐藥的原因之一，用CDKi可以克服舍哄，而CDKi主要也是可以靶向p-Rb,影響MYC表達(dá)宴凉。
個(gè)人收獲點(diǎn)：
- the expression of stemness markers such as ABCG2, Nanog, and Sox2 and decreased the expression of differentiation markers such as Keratin 4 and Keratin 13.
2.To further validate the role of ARID1A in the tumorigenic potential of SCC cells, a limiting dilution analysis was performed using KYSE410 cells expressing control or ARID1A shRNAs. 這里為了研究基因的致瘤能力，亦可反映腫瘤干性表悬，作者用不同濃度的細(xì)胞數(shù)進(jìn)行皮下成瘤弥锄，比較成瘤時(shí)間和大小。
![FY`MTL@[JWIDZ5}HWTKXH6.png
3.EMT:the expression of the mesenchymal markers CDH2, ZEB1, and ZEB2 .
EMT has been recognized as a contributor to chemoresistance in recent years [37];
4.we predicted the sequence logo of E2F1 using the JASPAR database [32] (Fig. 5a), and further analysis showed that E2F1 could bind to several sequences in the c-Myc promoter region (2?kb upstream of the transcriptional start site) (Fig. 5b).
![AIS89ZAOPC]L691%V2YQ3Y.png
