过表达miR-129-5p通过靶向MAPK1抑制宫颈癌HeLa细胞恶性生物行为

[摘要] 目的：探讨miR-129-5p 对宫颈癌HeLa细胞侵袭、迁移和EMT的作用及其机制。方法：选取宫颈癌HeLa细胞,利用生物信息学预测软件筛选miR-129-5p 的靶基因,双荧光素酶报告基因验证miR-129-5p 和MAPK1 的靶向关系。将miR-129-5p mimic、miR-129-5p inhibitor 和pcDNA-MAPK1 单独或联合转染到HeLa细胞,用qPCR检测HeLa细胞中miR-129-5p 和MAPK1 的表达水平,用Transwell、划痕愈合实验分别检测HeLa 细胞的侵袭、迁移能力,WB检测细胞中E-cadherin、N-cadherin、MAPK1、STAT3 和Bcl-xL的表达。构建裸鼠HeLa细胞皮下移植瘤模型,观察miR-129-5p 过表达对移植瘤生长的影响,WB检测移植瘤组织中EMT及MAPK1 通路相关蛋白的表达。结果：miR-129-5p 与MAPK1 在3’UTR区存在结合位点,过表达miR-129-5p 靶向抑制MAPK1（P<0.01）。与对照组相比,miR-129-5p mimic 组侵袭细胞数目减少（P<0.01）,划痕愈合率降低（均P<0.01）;细胞中Ecadherin表达上调而N-cadherin、MAPK1、STAT3 和Bcl-xL 表达下调（均P<0.01）;共转染MAPK1 可逆转上述现象。成功建立裸鼠HeLa 细胞移植瘤模型,与对照组相比,miR-128-3p mimic 组肿瘤质量减轻（P<0.01）;瘤组织中E-cadherin 表达水平上调而N-cadherin、MAPK1、STAT3 和Bcl-xL 的表达下调（均P<0.01）。结论：过表达miR-129-5p 通过靶向MAPK1 抑制宫颈癌HeLa细胞的侵袭、迁移和EMT。     

A Chromosome 17 Locus Engenders Frequency-Specific Non-Progressive Hearing Loss that Contributes to Age-Related Hearing Loss in Mice

The 129S6/SvEvTac (129S6) inbred mouse is known for its resistance to noise-induced hearing loss (NIHL). However, less is understood of its unique age-related hearing loss (AHL) phenotype and its potential relationship with the resistance to NIHL. Here, we studied the physiological characteristics of hearing loss in 129S6 and asked if noise resistance (NR) and AHL are genetically linked to the same chromosomal region. We used auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) to examine hearing sensitivity between 1 and 13 months of age of recombinant-inbred (congenic) mice with an NR phenotype. We identified a region of proximal chromosome (Chr) 17 (D17Mit143-D17Mit100) that contributes to a sensory, non-progressive hearing loss (NPHL) affecting exclusively the high-frequencies (>24 kHz) and maps to the nr1 locus on Chr 17. ABR experiments showed that 129S6 and CBA/CaJ F1 (CBACa) hybrid mice exhibit normal hearing, indicating that the hearing loss in 129S6 mice is inherited recessively. An allelic complementation test between the 129S6 and 101/H (101H) strains did not rescue hearing loss, suggesting genetic allelism between the nphl and phl1 loci of these strains, respectively. The hybrids had a milder hearing loss than either parental strain, which indicate a possible interaction with other genes in the mouse background or a digenic interaction between different genes that reside in the same genomic region. Our study defines a locus for nphl on Chr 17 affecting frequencies greater than 24 kHz.     

慢性收缩性心力衰竭患者血清miR-129表达与心功能的关系

目的 探讨慢性收缩性心力衰竭(CSHF)患者血清微小RNA-129(miR-129)表达水平并分析其与心功能指标的关系.方法 选取2016年5月-2018年10月在武汉市第六医院收治的103例CSHF患者为观察组,依据纽约心脏病协会(NYHA)标准将其分为三组:NYHAⅡ级组(33例)、NYHAⅢ级(28例)、NYHA...