血清微小RNA-141-3p、微小RNA-150-5p与鼻咽癌患者临床病理特征和放疗敏感性的关系研究

摘要 目的：探讨血清微小核糖核酸（miRNA）-141-3p、miR-150-5p与鼻咽癌（NPC）患者临床病理特征和放疗敏感性的关系。方法：收集2019年1月～2022年7月在我院接受放疗的92例NPC患者为NPC组,根据放疗疗效分为抵抗组和敏感组,另选取同期80名在我院体检的健康志愿者为对照组。比较对照组、NPC组血清miR-141-3p、miR-150-5p表达。分析NPC患者血清miR-141-3p、miR-150-5p表达与临床病理特征的关系。利用单因素和多因素Logistic回归分析NPC患者放疗抵抗的影响因素。结果：与对照组比较,NPC组血清miR-141-3p表达升高,miR-150-5p表达降低（P＜0.05）。NPC患者血清miR-141-3p、miR-150-5p表达在不同分化程度、TNM分期和淋巴结转移中比较有差异（P＜0.05）。92例NPC患者放疗抵抗发生率为22.83%（21/92）。单因素分析显示,抵抗组TNM分期Ⅲ～Ⅳa期和miR-141-3p ≥ 2.60比例高于敏感组,miR-150-5p ≥ 0.80比例低于敏感组（P＜0.05）。多因素Logistic回归分析显示,miR-141-3p ≥ 2.60为NPC患者放疗抵抗的独立危险因素,miR-150-5p ≥ 0.80为独立保护因素（P＜0.05）。结论：NPC患者血清miR-141-3p高表达,miR-150-5p低表达,与分化程度、TNM分期、淋巴结转移和放疗敏感性有关,有望成为NPC患者放疗抵抗的评价指标。     

甲状腺乳头状癌组织微小RNA-93-5p、微小RNA-98-5p表达与临床病理特征和增殖、侵袭基因表达的关系研究

摘要 目的：研究甲状腺乳头状癌（PTC）组织微小核糖核酸-93-5p（miR-93-5p）、微小RNA-98-5p（miR-98-5p）表达与临床病理特征和增殖、侵袭基因表达的关系。方法：选取2020年10月到2023年10月在广东省中医院行手术切除的PTC患者153例作为研究对象,收集术中切除的癌组织以及癌旁组织。检测并比较癌组织与癌旁组织miR-93-5p、miR-98-5p及增殖基因、侵袭基因mRNA表达水平,分析miR-93-5p及miR-98-5p表达与PTC患者临床病理特征的关系。利用Pearson法分析miR-93-5p、miR-98-5p表达水平与增殖基因、侵袭基因mRNA表达的相关性。结果：癌组织的miR-93-5p表达水平较癌旁组织更高,miR-98-5p表达水平较癌旁组织更低（P<0.05）。miR-93-5p高表达PTC患者TNM分期Ⅲ~Ⅳ期、有淋巴结转移及低分化的比例较miR-93-5p低表达PTC患者更高（P<0.05）。miR-98-5p低表达PTC患者TNM分期Ⅲ~Ⅳ期、有淋巴结转移及低分化的比例较miR-98-5p高表达PTC患者更高（P<0.05）。癌组织的增殖基因程序性细胞死亡因子4（PDCD4）及蛋白磷酸酶4调节亚基 （PP4R1）水平较癌旁组织更低（P<0.05）,侵袭基因金属蛋白酶解离素9（ADAM9）及Bcl-6共抑制因子样蛋白（BCORL1）水平较癌旁组织更高（P<0.05）。Pearson法分析结果显示,miR-93-5p表达与增殖基因PDCD4及PP4R1表达水平呈负相关,与侵袭基因ADAM9及BCORL1表达水平呈正相关。miR-98-5p表达水平与增殖基因PDCD4及PP4R1水平呈正相关,与侵袭基因ADAM9及BCORL1表达水平呈负相关。结论：PTC患者癌组织miR-93-5p表达升高,miR-98-5p表达降低,与TNM分期、淋巴结转移及分化程度等临床病理特征有关,还可促进PTC癌细胞增殖、侵袭。     

Distinct functions of maternal and somatic Pat1 protein paralogs

We previously identified Xenopus Pat1a (P100) as a member of the maternal CPEB RNP complex, whose components resemble those of P-(rocessing) bodies, and which is implicated in translational control in Xenopus oocytes. Database searches have identified Pat1a proteins in other vertebrates, as well as paralogous Pat1b proteins. Here we characterize Pat1 proteins, which have no readily discernable sequence features, in Xenopus oocytes, eggs, and early embryos and in human tissue culture cells. xPat1a and 1b have essentially mutually exclusive expression patterns in oogenesis and embryogenesis. xPat1a is degraded during meiotic maturation, via PEST-like regions, while xPat1b mRNA is translationally activated at GVBD by cytoplasmic polyadenylation. Pat1 proteins bind RNA in vitro, via a central domain, with a preference for G-rich sequences, including the NRAS 5′ UTR G-quadruplex-forming sequence. When tethered to reporter mRNA, both Pat proteins repress translation in oocytes. Indeed, both epitope-tagged proteins interact with the same components of the CPEB RNP complex, including CPEB, Xp54, eIF4E1b, Rap55B, and ePAB. However, examining endogenous protein interactions, we find that in oocytes only xPat1a is a bona fide component of the CPEB RNP, and that xPat1b resides in a separate large complex. In tissue culture cells, hPat1b localizes to P-bodies, while mPat1a-GFP is either found weakly in P-bodies or disperses P-bodies in a dominant-negative fashion. Altogether we conclude that Pat1a and Pat1b proteins have distinct functions, mediated in separate complexes. Pat1a is a translational repressor in oocytes in a CPEB-containing complex, and Pat1b is a component of P-bodies in somatic cells.     

Gastrodin relieves inflammation injury induced by lipopolysaccharides in MRC‐5 cells by up‐regulation of miR‐103

The beneficial function of gastrodin towards many inflammatory diseases has been identified. This study designed to see the influence of gastrodin in a cell model of chronic obstructive pulmonary disease (COPD). MRC‐5 cells were treated by LPS, before which gastrodin was administrated. The effects of gastrodin were evaluated by conducting CCK‐8, FITC‐PI double staining, Western blot, qRT‐PCR and ELISA. Besides this, the downstream effector and signalling were studied to decode how gastrodin exerted its function. And dual‐luciferase assay was used to detect the targeting link between miR‐103 and lipoprotein receptor‐related protein 1 (LRP1). LPS induced apoptosis and the release of MCP‐1, IL‐6 and TNF‐α in MRC‐5 cells. Pre‐treating MRC‐5 cells with gastrodin attenuated LPS‐induced cell damage. Meanwhile, p38/JNK and NF‐κB pathways induced by LPS were repressed by gastrodin. miR‐103 expression was elevated by gastrodin. Further, the protective functions of gastrodin were attenuated by miR‐103 silencing. And LRP1 was a target of miR‐103 and negatively regulated by miR‐103. The in vitro data illustrated the protective function of gastrodin in LPS‐injured MRC‐5 cells. Gastrodin exerted its function possibly by up‐regulating miR‐103 and modulating p38/JNK and NF‐κB pathways.     

Effect of c‐Ski on atrial remodelling in a rapid atrial pacing canine model

Atrial fibrosis is an important factor in the initiation and maintenance of atrial fibrillation (AF); therefore, understanding the pathogenesis of atrial fibrosis may reveal promising therapeutic targets for AF. In this study, we successfully established a rapid atrial pacing canine model and found that the inducibility and duration of AF were significantly reduced by the overexpression of c‐Ski, suggesting that this approach may have therapeutic effects. c‐Ski was found to be down‐regulated in the atrial tissues of the rapid atrial pacing canine model. We artificially up‐regulated c‐Ski expression with a c‐Ski–overexpressing adenovirus. Haematoxylin and eosin, Masson's trichrome and picrosirius red staining showed that c‐Ski overexpression alleviated atrial fibrosis. Furthermore, we found that the expression levels of collagen III and α‐SMA were higher in the groups of dogs subjected to right‐atrial pacing, and this increase was attenuated by c‐Ski overexpression. In addition, c‐Ski overexpression decreased the phosphorylation of smad2, smad3 and p38 MAPK (p38α and p38β) as well as the expression of TGF‐β1 in atrial tissues, as shown by a comparison of the right‐atrial pacing + c‐Ski‐overexpression group to the control group with right‐atrial pacing only. These results suggest that c‐Ski overexpression improves atrial remodelling in a rapid atrial pacing canine model by suppressing TGF‐β1–Smad signalling and p38 MAPK activation.     

LncRNA H19 ameliorates myocardial infarction‐induced myocardial injury and maladaptive cardiac remodelling by regulating KDM3A

Myocardial infarction (MI) remains the leading cause of morbidity and mortality worldwide, and novel therapeutic targets still need to be investigated to alleviate myocardial injury and the ensuing maladaptive cardiac remodelling. Accumulating studies have indicated that lncRNA H19 might exert a crucial regulatory effect on cardiovascular disease. In this study, we aimed to explore the biological function and molecular mechanism of H19 in MI. To investigate the biological functions of H19, miRNA‐22‐3p and KDM3A, gain‐ and loss‐of‐function experiments were performed. In addition, bioinformatics analysis, dual‐luciferase reporter assays, RNA immunoprecipitation (RIP) assays, RNA pull‐down assays, quantitative RT‐PCR and Western blot analyses as well as rescue experiments were conducted to reveal an underlying competitive endogenous RNA (ceRNA) mechanism. We found that H19 was significantly down‐regulated after MI. Functionally, enforced H19 expression dramatically reduced infarct size, improved cardiac performance and alleviated cardiac fibrosis by mitigating myocardial apoptosis and decreasing inflammation. However, H19 knockdown resulted in the opposite effects. Bioinformatics analysis and dual‐luciferase assays revealed that, mechanistically, miR‐22‐3p was a direct target of H19, which was also confirmed by RIP and RNA pull‐down assays in primary cardiomyocytes. In addition, bioinformatics analysis and dual‐luciferase reporter assays also demonstrated that miRNA‐22‐3p directly targeted the KDM3A gene. Moreover, subsequent rescue experiments further verified that H19 regulated the expression of KDM3A to ameliorate MI‐induced myocardial injury in a miR‐22‐3p‐dependent manner. The present study revealed the critical role of the lncRNAH19/miR‐22‐3p/KDM3A pathway in MI. These findings suggest that H19 may act as a potential biomarker and therapeutic target for MI.