miR4673 improves fitness profile of neoplastic cells by induction of autophagy.
miR4673 improves fitness profile of neoplastic cells by induction of autophagy.
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DOI：
10.1038/s41419-018-1088-6
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发表时间：
2018-10-19
影响因子：
9
通讯作者：
Farahani RM
中科院分区：
文献类型：
--
作者：
Dökümcü K;Simonian M;Farahani RM
肿瘤的治疗耐药主要归因于突变谱的逐渐演变。在这里，我们证明了microRNA介导的机制，有效地提高健身SKBR 3乳腺癌细胞的细胞质重编程。重编程由notch-1基因座转录的内源性miR 4673触发。miRNA下调cdk-18，一种调节周期细胞中M-G1转换的细胞周期蛋白依赖性激酶。抑制cdk-18触发线粒体自噬和自噬。由于高自噬通量，雌激素受体1+/孕激素受体+/p53+（Esr 1 +/Pr+/p53+）SKBR 3细胞被迫进入Esr 1 −/Prlow/p53−分布。增加线粒体自噬与p53蛋白酶体降解相结合，可短暂地将周期细胞阻滞在G 0，并增强SKBR 3群体的放射抗性。这些发现强调了非编码肿瘤抗性对癌症治疗的影响，这是由于miRNA介导的自噬重编程导致表型和基因型分离。
Therapeutic resistance of neoplasms is mainly attributed to gradual evolution of mutational profile. Here, we demonstrate a microRNA-mediated mechanism that effectively improves fitness of SKBR3 mammary carcinoma cells by cytoplasmic reprogramming. The reprogramming is triggered by endogenous miR4673 transcribed from notch-1 locus. The miRNA downregulates cdk-18, a cyclin-dependent kinase that regulates M-G1 transition in cycling cells. Suppression of cdk-18 triggers mitophagy and autophagy. Due to high autophagic flux, oestrogen receptor-1+/progesterone receptor+/p53+ (Esr1+/Pr+/p53+) SKBR3 cells are coerced into an Esr1−/Prlow/p53−profile. Increased mitophagy in combination with proteasomal degradation of p53 transiently arrests the cycling cells at G0 and enhances radio-resistance of the SKBR3 population. These findings highlight the impact on cancer therapy of non-encoded neoplastic resistance, arising as a consequence of miRNA-mediated autophagic reprogramming that uncouples phenotype and genotype.
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影响因子：
14.9
作者：
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
通讯作者：
Guegler KJ
影响因子：
16.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Chendrimada, TP;Gregory, RI;Shiekhattar, R
通讯作者：
Shiekhattar, R
影响因子：
20.3
作者：
Deriano, L;Guipaud, O;Delic, J
通讯作者：
Delic, J
影响因子：
3.3
作者：
Aerne, BL;Johnson, AL;Johnston, LH
通讯作者：
Johnston, LH