miR-199a-3p/Nme2在TGF-β1信号通路中的作用分析

通过microRNA芯片技术在小鼠GC-1 spg细胞中筛选发现microRNA-199a-3p(miR-199a-3p)受转化生长因子TGF-β1调节。为了进一步探讨二者的关系,通过基因克隆与载体构建技术、双荧光素酶报告基因检测及定量PCR实验,发现miR-199a-3p靶向识别肿瘤转移抑制基因2(Nme2)的3'非编码区(UTR)序列,且正向调控Nme2的表达。利用TGF-β1处理GC-1 spg细胞后,结果显示Nme2和miR-199a-3p在mRNA水平的表达均显著上调;进一步将miR-199a-3p和TGF-β1双重作用于GC-1 spg细胞后,结果表明Nme2的表达会明显增强,而且在TGF-β1通路中,miR-199a-3p被抑制的部分功能可能会被Nme2补偿。综上,miR-199a-3p对Nme2基因具有直接靶向识别和调控作用,且在参与TGF-β1信号通路的生物学效应中,二者在功能上相互关联。     

miR-411a-3p抑制羊驼黑色素细胞黑色素的生成

microRNA-411a-3p（miR-411a-3p）在不同毛色羊驼皮肤中差异表达,提示其可能在毛色形成中起调控作用。为证明miR-411a-3p在羊驼皮毛黑色素形成中的作用,本研究通过生物信息学预测及靶基因搜索,发现胰岛素样生长因子1受体（IGF1R）是miR-411a-3p的靶基因,继而构建了含Igf1r mRNA 3′-UTR的荧光素酶报告基因载体。报告基因转染结合报告酶活性测定证明,Igf1r是miR-411a-3p的靶基因。原位杂交显示,miR-411a-3p主要在羊驼黑色素细胞胞质中表达,提示其可能在黑色素细胞中具有重要作用。qRT-PCR揭示,棕色和黑色羊驼皮肤中miR-411a-3p表达量明显低于白色羊驼。qRT-PCR联合蛋白质印迹分析显示,在羊驼黑色素细胞过表达miR-411a-3p,伴随Igf1r下调,小眼畸形相关转录因子（Mitf）依赖的毛色基因酪氨酸酶（Tyr）、酪氨酸酶相关蛋白-2（Tyrp2）及黑色素表达水平明显下调。上述结果提示,miR-411a-3p可通过靶向抑制Igf1r负调控羊驼黑色素黑色素合成。该结果将加深我们对羊驼毛色形成机制的认识。     

circPVT1通过miR-24-3p/let-7a-5p/FSCN1轴促进鼻咽癌细胞侵袭迁移

目的 鼻咽癌是一种来源于鼻咽上皮的恶性肿瘤,其临床特征之一是易发生淋巴转移,但是目前鼻咽癌转移的分子机制尚未阐明。circPVT1是由PVT1基因2号外显子反向拼接形成的环状RNA (circRNA),在多种肿瘤中表达上调,本文探讨了circPVT1在鼻咽癌侵袭迁移中的作用和分子机制。方法 通过RT-qPCR检测circPVT1及其下游miRNA和FSCN1在鼻咽癌细胞的表达情况,Transwell和划痕愈合实验检测circPVT1对鼻咽癌细胞侵袭迁移的影响,RNA pull-down实验检测circPVT1结合的miRNA,双荧光素酶报告实验检测miR-24-3p和let-7a-5p靶向抑制FSCN1 mRNA表达。结果 在鼻咽癌细胞中过表达circPVT1可以促进鼻咽癌细胞侵袭迁移,而敲低circPVT1则可以抑制鼻咽癌细胞的侵袭迁移。进一步研究发现,circPVT1可以通过竞争性吸附miR-24-3p和let-7a-5p,上调FSCN1的表达,从而促进鼻咽癌细胞的侵袭迁移。结论 circPVT1通过miR-24-3p/let-7a-5p/FSCN1轴促进鼻咽癌细胞侵袭迁移,证实c...     

长非编码RNA ILF3-AS1通过调控miR-130a-3p/PTEN轴抑制宫颈癌细胞的增殖

ILF3反义RNA 1（ILF3 antisense RNA 1,ILF3-AS1）是一条定位于染色体19p13.2的lncRNA,它是白介素增强子结合因子3 (interleukin enhancer binding factor 3,ILF3)的反义RNA。ILF3-AS1在多种肿瘤发生发展中发挥关键作用,但其在宫颈癌中的作用尚无研究探讨。本文利用TCGA及GTEx数据库进行生物信息学分析提示,ILF3-AS1在宫颈癌组织中低表达（P<0.001）并与良好预后相关（P=0.045）。qRT-PCR结果显示,ILF3-AS1在宫颈癌组织及SiHa、HeLa、CaSki宫颈癌细胞系中表达较对照组均呈下降趋势。过表达ILF3-AS1可明显抑制宫颈癌细胞增殖活力及促进宫颈癌细胞凋亡。Star Base v3.0数据库分析提示,ILF3-AS1可靶向吸附miR-130a-3p;而miR-130a-3p可靶向结合PTEN。qRT-PCR检测显示,miR-130a-3p在宫颈癌中的表达量明显高于正常宫颈组织（P<0.01）。荧光素酶报告基因结果显示,ILF3-AS1可以与miR-130a-3p 特异性结合（P<0.01）。HeLa细胞过表达ILF3-AS1后,miR-130a-3p表达量明显下调（P<0.01）;在过表达ILF3-AS1细胞中,同时转染miR-130a-3p mimics,能部分逆转LF3-AS1对于细胞增殖的抑制作用（P<0.001）。HeLa细胞在过表达ILF3-AS1后,磷酸酶及张力蛋白同源物基因(phosphatase and tensin homolog deleted on chromosome ten,PTEN) mRNA（P<0.001）及蛋白质（P<0.001）表达量显著升高;当同时转染miR-130a-3p mimics,PTEN的 mRNA（P<0.001)及蛋白质（P<0.001）的表达升高被明显抑制。综上,ILF3-AS1可以作为miR-130a-3p的吸附海绵靶向调控PTEN表达,从而抑制宫颈癌细胞的增殖。     

miR-305-3p和miR-71-5p通过调控谷胱甘肽代谢途径参与斜纹夜蛾应对植物次生物质

昆虫和植物在长期进化过程中形成相互作用的关系。其中植物次生物质是植物防御昆虫的主要机制,而昆虫则以解毒酶来应对。为了发现可用于害虫防治的miRNA,通过对农业害虫斜纹夜蛾Spodoptera litura进食芥菜Brassica juncea后中肠的测序分析,获得了一系列差异表达的miRNA。通过生物信息学分析,发现斜纹夜蛾miR-305-3p靶向了谷胱甘肽代谢中的谷氨酸半胱氨酸连接酶的催化亚基(Slgclc),这是一个谷胱甘肽从头合成的限速酶;而miR-71-5p靶向调控gclc和解毒酶表达的转录因子SlNrf2。用芥菜的次生物质吲哚-3-甲醇处理斜纹夜蛾Spli-221细胞株后,实时荧光定量PCR证明Slgclc和SlNrf2表达上调,miR-305-3p和miR-71-5p表达下调。分别在斜纹夜蛾Spli-221细胞中超表达miR-305-3p及miR-71-5p mimics,Slgclc或SlNrf2转录水平下调,并且miR-71-5p mimic处理抑制了SlNrf2下游基因Slgclc和解毒酶谷胱甘肽S-转移酶(GSTs)的表达。结果表明:miR-305-3p和miR-71-5p响应植物次生物质而分别促进Slgclc和SlNrf2表达。然而双荧光素酶实验显示miR-305-3p并不与Slgclc直接结合,miR-71-5p也不与SlNrf2直接结合,推测miR-305-3p和miR-71-5p可能间接调控Slgclc和SlNrf2的表达。研究结果表明,斜纹夜蛾miR-305-3p和miR-71-5p通过调控解毒酶GSTs表达及其底物谷胱甘肽的生成,而参与昆虫抵抗植物次生物质。     

MiR-125a-5p抑制3T3-L1前体脂肪细胞分化

MicroRNAs(miRNAs) 是一类在脂肪组织发育中发挥重要作用的小非编码RNA. 为探明miR-125a-5p在3T3-L1前体脂肪细胞中的作用,采用实时qPCR检测了miR-125a-5p在小鼠各组织及3T3-L1前体脂肪细胞分化过程中的表达|使用经化学修饰的miR-125a-5p模拟物agomir及抑制剂antagomir转染3T3-L1前体脂肪细胞,采用实时qPCR 和 Western印迹检测成脂标志基因Pparγ和aP2的表达,油红O染色观察脂肪细胞脂质积累. 结果显示,miR-125-5p在小鼠脂肪组织中高丰度表达,在3T3-L1前体脂肪细胞分化过程中表达下降.过表达miR-125a-5p,与对照组相比,成脂标志基因Pparγ和aP2在mRNA和蛋白质水平均明显下降|油红O染色及定量结果显示脂质积累减少. 抑制剂处理结果显示,Pparγ和aP2在mRNA和蛋白质水平均有不同程度上升,但油红O染色及定量结果差异不显著. 以上结果表明,miR-125a-5p在脂肪细胞分化中发挥负调控作用.     

肝细胞癌组织miR-124-3p、miR-212-5p表达与PI3K/Akt信号通路和预后的关系研究

摘要 目的：探讨肝细胞癌组织中微小核糖核酸（miR）-124-3p、miR-212-5p表达与磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）信号通路和预后的关系。方法：选择2017年9月至2019年9月徐州医科大学附属医院肝胆外科收治的93例肝细胞癌患者,采用实时荧光定量聚合酶链反应（qRT-PCR）检测肝细胞癌组织中miR-124-3p、miR-212-5p、PI3K 信使RNA（mRNA）、Akt mRNA的表达。Pearson相关性分析miR-124-3p、miR-212-5p表达与PI3K/Akt信号通路相关mRNA表达的相关性。绘制Kaplan-Meier生存曲线,Log-Rank检验不同miR-124-3p、miR-212-5p表达肝细胞癌患者3年总生存率（OS）的差异。结果：肝细胞癌组织中miR-124-3p表达低于癌旁组织（P＜0.05）,miR-212-5p、PI3K mRNA、Akt mRNA表达高于癌旁组织（P＜0.05）。肝细胞癌组织中miR-124-3p表达与PI3K mRNA、Akt mRNA表达呈负相关（P＜0.05）,miR-212-5p表达与PI3K mRNA、Akt mRNA表达呈正相关（P＜0.05）。Ⅱa期、低分化患者肝细胞癌组织中miR-124-3p表达低于Ⅰa-Ⅰb期、中高分化患者（P＜0.05）,miR-212-5p表达高于Ⅰa-Ⅰb期、中高分化患者（P＜0.05）。随访期间死亡37例, miR-124-3p低表达组3年OS为42.55%,低于miR-124-3p高表达组的78.26%（P＜0.05）,miR-212-5p高表达组3年OS为50.00%,低于miR-212-5p低表达组的71.11%（P＜0.05）。结论：肝细胞癌组织中miR-124-3p表达下调,miR-212-5p表达上调,且与肝细胞癌PI3K/Akt信号通路激活,PI3K mRNA和Akt mRNA高表达,低分化,CNLC分期Ⅱa期以及低OS有关。     

miR-27a-3p通过靶向Sema7A调控病毒性心肌炎心肌细胞损伤的机制研究

目的探讨微小RNA-27a-3p(miR-27a-3p)过表达对病毒性心肌炎(VMC)细胞损伤的影响及其可能的作用机制。方法原代培养大鼠心肌细胞,柯萨奇B3病毒(CVB3)感染心肌细胞建立VMC模型(CVB3组)。正常心肌细胞作为对照组,分别将miR-NC、miR-27a-3p mimics、si-NC,si-Sema7A分别转染至CVB3感染的心肌细胞,记为CVB3+miR-NC组、CVB3+miR-27a-3p组、CVB3+si-NC组、CVB3+si-Sema7A组。分别将miR-27a-3p mimics与pcDNA,miR-27a-3p mimics与pcDNA-Sema7A共转染至CVB3感染的心肌细胞,记为CVB3+miR-27a-3p+pcDNA组、CVB3+miR-27a-3p+pcDNA-Sema7A组。采用实时荧光定量聚合酶链反应(qRT-PCR)与Western blot法分别检测细胞中miR-27a-3p、信号蛋白7A(Sema7A)的表达水平;流式细胞术检测miR-27a-3p过表达或干扰Sema7A表达后心肌细胞的凋亡率;酶联免疫吸附(ELISA)法检测细胞中肿瘤坏死因子-α(TNF-α)、白细胞介素-1(IL-1)的含量;双荧光素酶报告基因验证miR-27a-3p与Sema7A的靶向关系;Western blot检测B淋巴细胞瘤-2相关蛋白(Bax)、活化的含半胱氨酸的天冬氨酸蛋白水解酶3(cleaved caspase-3)、B淋巴细胞瘤-2(Bcl-2)蛋白表达。两组间比较采用独立样本t检验。结果与对照组比较,CVB3组miR-27a-3p的表达水平(1.01±0.09比0.42±0.04)降低,Sema7A的mRNA和蛋白表达水平(1.02±0.09比2.15±0.21、0.43±0.04比0.94±0.09)升高,TNF-α、IL-1水平[(403.56±38.16)pg/mL比(1156.48±63.59)pg/mL>(29.45±3.54)pg/mL比(136.57±12.47)pg/mL]升高,细胞凋亡率[(5.36±0.54)%比(24.58±2.14)%]升高,Bax、cleaved caspase-3的表达水平升高,Bcl-2的表达水平降低(P均<0.05);与CVB3+miR-NC组比较,CVB3+miR-27a-3p组TNF-α,IL-1水平[(1187.69±71.42)pg/mL比(516.28±48.31)pg/mL、(147.25±14.05)pg/mL比(43.68±5.02)pg/mL]和细胞凋亡率[(26.38±2.55)%比(10.24±1.15)%]降低,Bax、cleaved caspase-3表达水平降低,Bcl-2表达水平升高(P均<0.05);双荧光素酶报告实验证实miR-27a-3p可靶向调控Sema7A的表达;Sema7A过表达可逆转miR-27a-3p过表达对CVB3诱导的VMC细胞损伤的作用。结论miR-27a-3p过表达可降低VMC细胞中炎症因子的表达及抑制细胞凋亡从而减轻心肌损伤,其作用机制可能与靶向调控Sema7A的表达有关。     

miR-196a-5p对3T3-L1前脂肪细胞增殖和分化的影响效应

目的:探究miR-196a-5p对小鼠前体脂肪细胞增殖、分化的影响及其潜在的分子机制。方法:(1)构建小鼠肥胖模型,RT-PCR检测脂肪组织中miR-196a-5p表达量;(2)鸡尾酒法诱导3T3-L1前脂肪细胞分化,RT-PCR检测分化过程中miR-196a-5p的表达变化;(3)合成miR-196a-5p mimics和inhibitors转染3T3-L1细胞,以CCK8、EdU试剂盒检测miR-196a-5p对3T3-L1前脂肪细胞增殖的影响作用;(4)运用油红O染色、甘油三酯测定评估miR-196a-5p对3T3-L1细胞分化的影响;(5) RT-PCR检测miR-196a-5p对前脂肪细胞增殖、分化相关基因的影响;(6)结合前人文献,运用生物信息软件、萤光素酶报告系统对miR-196a-5p调控脂肪细胞分化的靶基因进行筛选和验证。结果:(1) miR-196a-5p在肥胖小鼠脂肪组织中高表达,在3T3-L1前脂肪细胞分化过程中先升高后下降;(2)与阴性对照组相比,mimics转染抑制了3T3-L1细胞增殖,inhibitors转染促进了3T3-L1细胞增殖;(3)与阴性对照组相比,mimics组积累了大量油红着色的脂滴,甘油三酯含量增多,而inhibitors组的脂滴少而小,甘油三酯含量相对降低;(4)与阴性对照组相比,mimics转染抑制了增殖标志基因Cyclin D1、Cyclin E、CDK2和CDK4表达,促进了分化标志基因PPARγ、C/EBPα、LPL、aP2等的表达,inhibitors转染则表现出与mimics转染相反的作用;(5) miR-196a-5p可显著抑制野生型MAP4K3和MAPK1 3'UTR萤光素酶活性,而突变绑定位点可废除该抑制效应。结论:miR-196a-5p不仅可抑制3T3-L1前脂肪细胞增殖,还可促进其诱导分化、沉积脂滴;miR-196a-5p可能通过靶向调节MAP4K3和MAPK1来介导3T3-L1前脂肪细胞分化。     

支气管哮喘患者血清miR-29a-3p、miR-98-5p表达水平与肺功能、气道炎症和糖皮质激素治疗敏感性的关系研究

摘要 目的：探讨支气管哮喘（BA）患者血清微小核糖核酸（miR）-29a-3p、miR-98-5p表达水平与肺功能、气道炎症和糖皮质激素（GC）治疗敏感性的关系。方法：选取2020年1月～2022年1月潍坊市人民医院收治的150例BA患者为BA组,根据BA患者GC治疗敏感性将其分为抵抗组43例和敏感组107例,另选取同期57名体检健康者为对照组。收集BA组、对照组肺功能和气道炎症指标资料,采用实时荧光定量逆转录聚合酶链式反应（qRT-PCR）检测两组血清miR-29a-3p、miR-98-5p表达水平。通过Spearman相关性分析BA患者血清miR-29a-3p、miR-98-5p表达水平与肺功能和气道炎症指标的相关性,单因素和多因素Logistic回归分析BA患者GC治疗抵抗的影响因素。结果：与对照组比较,BA组血清miR-29a-3p、miR-98-5p表达水平和第1秒用力呼气容积占预计值百分比（FEV₁％）、第1秒用力呼气容积/用力肺活量（FEV₁/FVC）、峰值呼气流速（PEF）降低,呼出气一氧化氮（FeNO）水平升高（P均＜0.05）。Spearman相关性分析显示,BA患者血清miR-29a-3p、miR-98-5p表达水平与FEV₁％、FEV₁/FVC、PEF呈正相关,与FeNO水平呈负相关（P均＜0.05）。单因素分析显示,抵抗组体质指数＞24 kg/m²、吸烟比例高于敏感组,血清miR-29a-3p、miR-98-5p表达水平低于敏感组（P＜0.05）。多因素Logistic回归分析显示,体质指数＞24 kg/m²、吸烟为BA患者GC治疗抵抗的独立危险因素,血清miR-29a-3p、miR-98-5p表达水平升高为其独立保护因素（P均＜0.05）。结论：BA患者血清miR-29a-3p、miR-98-5p水平降低,与肺功能下降、气道炎症和GC治疗抵抗有关。     

Circulating miR-3613-5p but not miR-125b-5p,miR-199a-3p,and miR-451a are biomarkers of endometriosis

ObjectiveThis study aimed to assess the utility of circulating miR-125b-5p, miR-199a-3p, miR-451a, and miR-3613-5p as biomarkers of endometriosis.Study designPatients with stage III or IV of endometriosis according to the revised American Society of Reproductive Medicine (rASRM) staging classification, as well as control women, were recruited. We created a prospective study conducted on a group of 48 patients (n = 25 controls, n = 24 endometriosis) who had laparoscopic surgery. Blood samples were taken and plasma miRNA levels were measured by quantitative real-time polymerase chain reaction (RT-qPCR) and assessed with AUC and ROC curves.ResultsMiR-451a and miR-3613-5p were significantly decreased in the plasma of endometriosis patients. miR-451a had a receiver-operating characteristic (ROC) area under the curve 0.8283 and miR-3613-5p had a ROC area under the curve 0.7617. The concentration of circulating miR-125b-5p and miR-199-3p did not differ between endometriosis patients and controls. Plasma miRNA levels did not change with BMI, smoking status, fertility problems, or menstrual pain according to the VAS scale (p > 0.05).ConclusionCirculating miR-451a and miR-3613-5p levels significantly differed between endometriosis and controls. However, the levels of miR-451a were discordant with previous studies. Therefore, miR-3613-5p may have better potential as the endometriosis biomarker. Circulating miR-125b-5p and miR-199a-3p cannot be used as reliable markers of endometriosis.     

miR-103a-2-5p/miR-30c-1-3p inhibits the progression of prostate cancer resistance to androgen ablation therapy via targeting androgen receptor variant 7

Androgens and androgen receptors are vital factors involved in prostate cancer progression, and androgen ablation therapies are commonly used to treat advanced prostate cancer. However, the acquisition of androgen ablation therapy resistance remains a challenge. Recently, androgen receptor splicing variants lacking the ligand-binding domain have been reported to play a critical role in the acquisition of androgen ablation therapy resistance. In the present study, we revealed that the messenger RNA expression and the protein levels of an androgen receptor variant 7 (AR-V7) were higher in prostate cancer tissue samples and in the AR-positive prostate cancer cell line, VCaP. In contrast, microRNA (miR)-30c-1-3p/miR-103a-2-5p expression was significantly downregulated in tumor tissues and cells. miR-30c-1-3p/miR-103a-2-5p overexpression could inhibit AR-V7 expression, suppress VCaP cell growth, and inhibit AR-V7 downstream factor expression by directly targeting the 3′-untranslated region of AR-V7. Under enzalutamide (Enza) treatment, the effects of AR-V7 overexpression were the opposite of those of miR-103a-2-5p/miR-30c-1-3p overexpression; more importantly, the effects of miR-103a-2-5p/miR-30c-1-3p overexpression could be significantly reversed by AR-V7 overexpression under Enza. In summary, we demonstrated a novel mechanism of the miR-30c-1-3p/miR-103a-2-5p/AR-V7 axis modulating the cell proliferation of AR-positive prostate cancer cells via AR downstream targets. The clinical application of miR-30c-1-3p/miR-103a-2-5p needs further in vivo validation.     

miR-15a-5p和miR-16-5p在骨肉瘤组织中的表达分析

目的:使用microRNAs基因芯片及实时定量PCR法测定骨肉瘤组织中miR-15a-5p和miR-16-5p的相对表达含量,并与瘤旁组织对比,分析骨肉瘤细胞内miR-15a-5p和miR-16-5p的表达变化。方法:选取34例骨肉瘤组织蜡块样本,使用microRNAs基因芯片观察miR-15a-5p和miR-16-5p在骨肉瘤和瘤旁组织内的表达差异;实时定量PCR法测定骨肉瘤组织和瘤旁组织中miR-15a-5p和miR-16-5p的相对表达含量,并将两种结果对比分析。结果:microRNAs基因芯片结果显示,在骨肉瘤组织中,miR-15a-5p在肿瘤中的表达较瘤旁组织低1.79倍,miR-16-5p较瘤旁组织低1.62倍。实时定量PCR实验结果表明,miR-15a-5p和miR-16-5p表达较瘤旁组织降低,差异有统计学意义(P0.05)。经过统计学计算,miR-15a-5p在肿瘤中的表达较瘤旁组织低3.14倍,miR-16-5p较瘤旁组织低5.65倍。结论:在骨肉瘤中,miR-15a-5p和miR-16-5p表达含量降低,提示这两种microRNAs在骨肉瘤中可能做为抑癌因子存在。     

Long noncoding RNA PVT1 facilitates high glucose-induced cardiomyocyte death through the miR-23a-3p/CASP10 axis

Dilated cardiomyopathy (DCM) is the leading cause of morbidity and mortality in diabetic patients. Long noncoding RNA plasmacytoma variant translocation 1 (PVT1) has been shown to be related to the pathogenesis of DCM. However, the mechanism by which PVT1 regulates DCM pathogenesis is unclear. High glucose level was employed to construct a DCM cell model in vitro. Cell viability was determined via cell counting kit-8 assay. The level of lactate dehydrogenase (LDH) was measured with the corresponding kit. Expression levels of PVT1, miR-23a-3p, and caspase-10 (CASP10) messenger RNA were evaluated with a quantitative real-time polymerase chain reaction. Cell apoptosis was assessed by flow cytometry assay. Protein levels of B-cell lymphoma 2-associated X (Bax), cleaved-caspase-3 (cleaved-casp-3), and CASP10 were examined via western blot analysis. The relationship between PVT1 or CASP10 and miR-23a-3p was verified with dual-luciferase reporter assay. We observed that PVT1 and CASP10 were upregulated while miR-23a-3p was downregulated in high glucose-induced cardiomyocytes. High glucose levels repressed cardiomyocyte activity and induced cardiomyocyte apoptosis, but this influence was antagonized by PVT1 knockdown or miR-23a-3p overexpression. Furthermore, PVT1 acted as a sponge for miR-23a-3p, and miR-23a-3p inhibition counterbalanced the influence of PVT1 silencing on viability and apoptosis of cardiomyocytes under high glucose level treatment. PVT1 could increase CASP10 expression via sponging miR-23a-3p. In conclusion, PVT1 acted as a deleterious lncRNA in DCM. PVT1 facilitated cardiomyocyte death by regulating the miR-23a-3p/CASP10, which offered a new mechanism to comprehend the pathogenesis of DCM.     

p53 induces miR-199a-3p to suppress mechanistic target of rapamycin activation in cisplatin-induced acute kidney injury

How p53 participates in acute kidney injury (AKI) progress and what are the underlying mechanisms remain illusive. For this issue, it is important to probe into the role of p53 in cisplatin-induced AKI. We find that p53 was upregulated in cisplatin-induced AKI, yet, pifithrin-α inhibites the p53 expression to attenuated renal injury and cell apoptosis both in vivo cisplatin-induced AKI mice and in vitro HK-2 human renal tubular epithelial cells. To knock down p53 by siRNA significantly decreased the miRNA, miR-199a-3p, expression in HK-2 cells. Blockade of miR-199a-3p significantly reduced cisplatin-induced cell apoptosis and inhibited caspase-3 activity. Mechanistically, we identified that miR-199a-3p directly bound to mechanistic target of rapamycin (mTOR) 3′-untranslated region and overexpressed miR-199a-3p reduce the expression and phosphorylation of mTOR. Furthermore, we demonstrated that p53 inhibited mTOR activation through activating miR-199a-3p. In conclusion, our findings reveal that p53, upregulating the expression of miR-199a-3p affects the progress of cisplatin-induced AKI, which might provide a promising therapeutic target of AKI.     

miR-125a-3p suppresses the growth and progression of papillary thyroid carcinoma cell by targeting MMP11

The dysregulation of miR-125a-3p has been observed in multiple tumor types. Nevertheless, the function of miR-125a-3p in papillary thyroid carcinoma (PTC) is yet to be explored. Herein, we find that miR-125a-3p is markedly downregulated in PTC tissues, and its level is inversely related to the histological grade of PTC. Upregulation of miR-125a-3p suppresses the pulmonary metastatic ability as well as the tumor growth of PTC cell in vivo. Consistently, the colony formation ability and other metastasis-related traits of PTC cell are inhibited by miR-125a-3p transfection in vitro. In addition, we identify that matrix metalloprotease 11 (MMP11) is the direct target gene of miR-125a-3p, and that miR-125a-3p inhibits cell viability, migration, and invasiveness of PTC cell by reducing MMP11 expression in vitro. Together, these data testify that the miR-125a-3p/MMP11 axis plays vital roles in the growth and progression of human PTC cells.