Profilin 1, negatively regulated by microRNA-19a-3p,serves as a tumor suppressor in human hepatocellular carcinoma

Profilin 1 (PFN1) is a critical actin-regulatory protein; however, its functional role in hepatocellular carcinoma (HCC) progression remains to be further elucidated. In the present study, we observed that the expression levels of PFN1 were significantly decreased in HCC tissues and cell lines. Low PFN1 expression was significantly correlated with aggressive clinicopathological characteristics and poor prognosis of HCC patients. Further in vitro experiments demonstrated that overexpression of PFN1 remarkably inhibited the proliferation, migration, invasion and EMT of HCC cells. Moreover, we also found that PFN1 was a direct target gene of miR-19a-3p, and in HCC tissues, and there was a significantly inverse correlation between PFN1 mRNA and miR-19a-3p expression. Collectively, our results showed that PFN1 functions as a tumor suppressor in HCC, and might serve as a diagnostic and therapeutic target for HCC patients.     

Donor characteristics do not influence transfusion-related acute lung injury incidence in a secondary analysis of two case-control studies

Objective

To investigate the relation between donor characteristics and TRALI incidence.

胰腺导管腺癌中microRNA-21与TGF-β1信号通路相关

目的：对胰腺导管腺癌样本进行基因分析,筛选与胰腺导管腺癌相关的microRNA(miRNA),并初步分析目标miRNA与胰腺癌转化生长因子-β1(TGF-β1)信号通路的相关性。方法：收集在海南省中医院住院的胰腺导管癌患者术前外周静脉血血清标本19份,健康体检人群的外周静脉血血清标本21份作为非胰腺导管癌对照组。利用GCBI(Gene-Cloud Biotechnology Information)数据平台筛选与胰腺导管腺癌样本有关的基因并对其进行生物信息学分析,将筛选出的基因作为研究对象,用real-time PCR和蛋白质印迹法验证该基因在胰腺导管腺癌中的表达。通过改变胰腺导管腺癌细胞中该基因的表达水平观察其与TGF-β1之间的关系。结果：通过聚类分析和基因功能富集分析筛选出miRNA-21为胰腺导管癌相关基因。MiRNA-21在胰腺导管腺癌患者体内高表达。在miRNA-21过表达的PANC-1细胞中,TGF-β1表达受到抑制;但当miRNA-21的表达受到抑制时,TGF-β1的表达明显上升。结论：MiRNA-21在胰腺导管腺癌患者体内高表达,可调控TGF-β1的表达,从而参与胰腺导管腺癌的发生发展。     

前列腺癌患者血清miRNA 194和miRNA 206表达水平及临床意义

【摘要】 目的 探讨前列腺癌（PCa）患者血清miRNA 194和miRNA 206表达水平及临床意义。方法 选取2008年5月～2014年12月我院收治的108例PCa患者为PCa组,以及同期就诊的60例良性前列腺增生（BPH）患者为BPH组、前列腺正常者60例为正常组,分析所有纳入研究者的临床及随访资料,记录年龄等一般临床资料和血清miRNA 194和miRNA 206等指标水平及PCa患者肿瘤及预后情况,并比较不同PCa患者间上述资料的差异性。结果 BPH组和PCa组患者血清miRNA 206水平较正常组低（P＜005）,而血清PSA水平和miRNA 194较正常组高(P＜005);且PCa患者其血清miRN A 206水平较BHP患者更低,而血清PSA和miRNA 194水平则更高（P＜005）;Gleason 评分大于7分、临床分期T3~T4期以及出现淋巴结转移和术后复发的PCa患者其血清miRNA 206水平均显著降低,而血清miRNA 194显著升高（P＜005）;死亡患者血清miRNA 206水平均显著低于生存者,而血清miRNA 194水平显著高于生存者（P＜005）;经 Log rank检验,Gleason 评分大于7分、临床分期T3~T4期、出现淋巴结转移、术后复发以及血清miR NA 194水平升高和miRNA 206水平降低的PCa患者其生存时间均较短（P＜005）;经多因素Cox 比例风险回归模型分析,淋巴结转移、术后复发以及血清miRNA 194升高和miRNA 206水平降低均为影响PCa患者预后的独立影响因素（P＜005）。结论 血清miRNA 194在PCa患者中显著上升,而血清miRNA 206水平显著下降,且血清miRNA 194的上升和miRNA 206的下降均为影响PCa患者预后的独立影响因素,因此临床上可将其作为评估PCa患者病情及预后的有效指标。     

MiR-30a-5p通过泛素水解酶22抑制人宫颈癌细胞上皮-间质转化功能

【目的】研究microRNA-30a-5p（miR-30a-5p）对人宫颈癌Hela细胞上皮-间质转化功能的影响及其相关机制。【方法】宫颈癌Hela细胞株分别转染目的mir的模拟物和阴性对照模拟物,分别以30a-5p组、NC组命名并标记细胞。同时,以未经过处理的Hela细胞作为对照（Control组）。分别用逆转录-聚合酶链反应法检测各组宫颈癌细胞的miR-30a-5p含量。Transwell实验检测3组细胞迁移能力和侵袭能力。Western-blot法检测3组细胞神经-钙粘素（N-cadherin）、α-连环蛋白（α-Catenin）和泛素水解酶22（USP22）表达水平。运用生物信息学方法预测miR-30a-5p的靶基因。采用Western blot法检测USP22过表达对miR-30a-5p抑制EMT的拮抗作用。双荧光素酶实验检测miR-30a-5p与USP22的关系。建立皮下移植瘤模型观察miR-30a-5p的体内作用。【结果】30a-5p组宫颈癌细胞miR-30a-5p的表达水平明显上调,表达水平为Control组的853.82（862.26~843.11）倍（P＜0.01）。30a-5p组侵袭细胞数量8.17（8.32~8.03）明显低于Control组（P＜0.01）。30a-5p组细胞N-cadherin蛋白的细胞内含量明显下降,α-Catenin蛋白的细胞内含量明显上升,USP22蛋白表达量明显降低。合并USP22过表达处理的30a-5p组宫颈癌细胞中N-cadherin蛋白表达量明显升高,α-Catenin蛋白表达量明显降低。双荧光素酶检验结果显示USP22为miR-30a-5p的下游靶基因（P＜0.01）。30a-5p组皮下移植瘤明显小于Control组（P＜0.01）。与Control组肿瘤组织相比,30a-5p组肿瘤组织miR-30a-5p的相对含量升高,USP22蛋白含量降低,N-cadherin蛋白的含量降低,α-Catenin蛋白含量升高。【结论】miR-30a-5p在宫颈癌Hela细胞中,可能通过靶向识别下游靶基因USP22,进而抑制其翻译。最终实现对宫颈癌细胞EMT过程的抑制。     

Dysregulation of microRNA-106a-5p-RUNX1 axis associates with clinical progression and prognosis of osteosarcoma patients

MicroRNA-106a-5p (miR-106a-5p) functions as a tumor suppressor in osteosarcoma cells. Here, we aimed to identify novel target genes of miR-106a-5p in osteosarcoma, as well as to investigate their prognostic value and the biological functions. At first, the mammalian runt-related factor 1 (RUNX1) was identified as one of the target genes of miR-106a-5p in osteosarcoma cells by luciferase reporter gene assay, real-time quantitative RT-PCR and Western blot analysis. Then, the expression levels of miR-106a-5p and RUNX1 in osteosarcoma tissues were detected, and their associations with clinicopathological features and patients' prognosis were statistically analyzed. Compared with adjacent non-cancerous tissues, miR-106a-5p and RUNX1 mRNA/protein expression in osteosarcoma tissues were significantly decreased and increased, respectively (all P < 0.01). Low miR-106a-5p, high RUNX1 and miR-106a-5p-low/RUNX1-high expression in osteosarcoma tissues were all significantly associated with advanced Enneking stage, positive metastasis and shorter overall survival (all P < 0.05). Moreover, miR-106a-5p and RUNX1 expression, alone or in combination, were identified as independent prognostic factors for osteosarcoma patients' overall survival. Functionally, the enforced expression of miR-106a-5p significantly suppressed proliferation and invasion of osteosarcoma cells, while the overexpression of RUNX1 effectively reversed its suppressive roles. In conclusion, our findings show the dysregulation of miR-106a-5p-RUNX1 axis in human osteosarcoma tissues and suggest its crucial roles in cancer progression and patients' prognosis. More interestingly, miR-106a-5p may function as a tumor suppressor in osteosarcoma cells via regulating its target gene RUNX1.