Cancer-associated fibroblast-derived exosomal microRNA-20a suppresses the PTEN/PI3K-AKT pathway to promote the progression and chemoresistance of non-small cell lung cancer.
Cancer-associated fibroblast-derived exosomal microRNA-20a suppresses the PTEN/PI3K-AKT pathway to promote the progression and chemoresistance of non-small cell lung cancer.
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癌症相关成纤维细胞衍生的外泌体 microRNA-20a 抑制 PTEN/PI3K-AKT 通路，促进非小细胞肺癌的进展和化疗耐药
DOI：
10.1002/ctm2.989
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发表时间：
2022-07
影响因子：
10.6
通讯作者：
中科院分区：
文献类型：
--
作者：
癌症相关成纤维细胞（CAF）有助于整体肿瘤进展。在目前的调查中，我们探索了这些CAF衍生的外泌体中microRNA-20 a（miR-20 a）影响非小细胞肺癌（NSCLC）进展的能力。从NSCLC患者肿瘤和癌旁肺组织样品中收集正常组织相关成纤维细胞（NAF）和CAF。然后通过蛋白质印迹、纳米颗粒跟踪分析和透射电子显微镜对来自这些细胞的外泌体进行表征。通过qPCR和荧光原位杂交（FISH）评估miR-20 a的表达。CCK-8、EdU摄取和集落形成评估用于评价肿瘤增殖，同时进行Hoechst染色以监测肿瘤细胞的体外凋亡死亡。在裸鼠中建立的异种移植肿瘤模型也用于评价体内肿瘤反应。CAF衍生的外泌体表现出miR-20 a上调，并促进NSCLC细胞增殖和对顺铂（DDP）的耐药性。从机制上讲，发现CAF衍生的外泌体将miR-20 a传递到肿瘤细胞，其中它能够靶向PTEN以增强DDP抗性和增殖。外泌体来源的miR-20 a处理后相关的PTEN下调增强了PI 3 K/AKT通路的激活。所取得的结果解释了CAF可以释放能够促进NSCLC进展和化疗耐药性的含miR-20 a的外泌体，强调该途径是NSCLC的可能治疗靶点。CAFs来源的外泌体miR-20 a促进NSCLC的进展。CAF衍生的外泌体miR-20 a促进NSCLC的化学抗性。PTEN是miR-20 a的靶基因。4. miRNA-20 a抑制PTEN/PI 3 K-AKT通路。
Cancer‐associated fibroblasts (CAFs) contributes to overall tumor progression. In the current survey, we explored the ability of microRNA‐20a (miR‐20a) within these CAF‐derived exosomes to influence non‐small‐cell lung cancer (NSCLC) progression. Normal tissue‐associated fibroblasts (NAFs) and CAFs were collected from samples of NSCLC patient tumors and paracancerous lung tissues. Exosomes derived from these cells were then characterized via Western blotting, nanoparticle tracking analyses, and transmission electron microscopy. The expression of miR‐20a was assessed via qPCR and fluorescence in situ hybridization (FISH). CCK‐8, EdU uptake, and colony formation assessments were used for evaluating tumor proliferation, while Hoechst staining was performed to monitor the in vitro apoptotic death of tumor cells. A model of xenograft tumor established in nude mice was also used to evaluate in vivo tumor responses. CAF‐derived exosomes exhibited miR‐20a upregulation and promoted NSCLC cell proliferation and resistance to cisplatin (DDP). Mechanistically, CAF‐derived exosomes were discovered to transmit miR‐20a to tumor cells wherein it was able to target PTEN to enhance DDP resistance and proliferation. Associated PTEN downregulation following exosome‐derived miR‐20a treatment enhanced PI3K/AKT pathway activation. The achieved outcomes explain that CAFs can release miR‐20a‐containing exosomes capable of promoting NSCLC progression and chemoresistance, highlighting this pathway as a possible therapeutic target in NSCLC. CAFs‐derived exosomal miR‐20a promotes the progression of NSCLC. CAFs‐derived exosomal miR‐20a promotes chemoresistance of NSCLC. PTEN is a target gene of miR‐20a. 4. miRNA‐20a suppresses the PTEN/PI3K‐AKT pathway.
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DOI：
10.1016/j.jconrel.2015.07.030
发表时间：
2015-12-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Batrakova EV;Kim MS
通讯作者：
Kim MS
影响因子：
3.7
作者：
Lange T;Stracke S;Rettig R;Lendeckel U;Kuhn J;Schlüter R;Rippe V;Endlich K;Endlich N
通讯作者：
Endlich N
影响因子：
14.9
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Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
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Guegler KJ
Mir-20a-5p诱导的WTX缺乏通过调节PI3K/AKT信号通路促进胃癌进展
DOI：
10.1186/s13046-020-01718-4
发表时间：
2020-10-08
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Li J;Ye D;Shen P;Liu X;Zhou P;Zhu G;Xu Y;Fu Y;Li X;Sun J;Xu J;Zhang Q
通讯作者：
Zhang Q
影响因子：
14.8
作者：
Huang, Da Wei;Sherman, Brad T.;Lempicki, Richard A.
通讯作者：
Lempicki, Richard A.