miR-146a在胰腺癌组织中的表达及临床意义

[摘要] 目的 分析20例胰腺癌及胰腺良性病变组织中miR-146a的表达差异,评价miR-146a在胰腺癌中表达的临床意义及其价值。方法 收集笔者医院14例胰腺癌患者手术标本的癌组织,6例胰腺良性病变组织作为对照。采用Agilent 人microRNA寡核苷酸基因芯片(V12.0)在基因组范围内检测20例组织标本的miR-146a表达,并分析其与胰腺癌临床病理参数的关系。结果 胰腺癌组织中miR-146a的表达显著高于胰腺良性病变组织,差异有统计学意义(P =0.003), miR-146a在胰腺癌组织中的表达与患者年龄、性别、吸烟、临床分期、局部淋巴结转移,远处转移、CA199浓度、肿瘤分化程度、肿瘤分期,神经束膜侵犯、脉管侵犯均无相关性(P >0.05)。结论 miR-146a在胰腺癌的发生、发展过程可能发挥重要作用并可能成为胰腺癌新的肿瘤标记物或预后因子。     

miR-155和miR-30a在胃癌组织中的表达及临床意义

目的 探讨胃癌组织和癌旁组织miR-155和miR-30a的表达差异及其临床意义.方法 收集手术切除的胃癌标本52例,采用实时荧光定量逆转录-聚合酶链反应( RT-qPCR)检测癌及癌旁组织标本miR-155和miR-30a的表达水平,分析其与临床病理的关系.结果 miR-155在胃癌组织中表达量(0.84 ±2.27)显著高于其在配对癌旁组织中的表达值(0.28 ±0.56,P＜0.05);miR-155高表达与淋巴结转移有关(P＜0.05).miR-30a在胃癌组织中表达量(3.16±8.11)显著低于其在配对癌旁组织中的表达值(15.87±35.58,P＜0.05).miR-30a的低表达与肿瘤侵犯层次、淋巴结转移有关(P＜0.05).结论 miR-155和miR-30a与胃癌发生发展密切相关,可能成为胃癌的潜在诊断及治疗靶点.     

miR-153在胃癌组织中的表达及其临床意义

目的:探讨miR-153在胃癌中的表达及其临床意义。方法:收集49例胃癌根治术后组织和配对癌旁正常组织标本,采用实时荧光定量-聚合酶链反应(RT-qPCR)检测miR-153的表达水平,并分析其与胃癌临床TNM分期、肿瘤大小、分化程度、淋巴结转移等临床病理参数之间的关系。结果:miR-153在胃癌组织中的表达量显著低于相应癌旁正常组织(P0.01),miR-153的表达量与胃癌淋巴结转移有关(P0.05),与民族、性别、年龄、分化程度、肿瘤大小、临床TNM分期等病理参数无关(P0.05)。结论:miR-153在胃癌组织中低表达,提示miR-153可能与胃癌的发生发展有关。     

miR-21在骨肉瘤中的表达及其临床意义

[目的]探讨miR-21在骨肉瘤中的表达并分析其与临床病理之间的联系。[方法]本文通过实时定量PCR方法检测42例骨肉瘤组织(包括12例来自同一患者的原发骨肉瘤组织和转移肿瘤组织)和来自同一患者的邻近正常骨组织中miR-21的表达并评估miR-21的临床相关性。[结果]miR-21在所有的组织中都有表达,且在肿瘤组织中比在正常组织中有明显的高表达(P=0.013),此外,miR-21在转移的肿瘤组织中比在同一样本中的原发肿瘤组织中高表达(P=0.002),另外,miR-21高表达的患者有着显著更差预后(P=0.016)。[结论]miR-21高表达潜在的导致转移,其可以作为骨肉瘤患者预后的一个指标。     

miR-155在结肠癌组织中的表达及其临床意义

目的 研究miR-155在结肠癌组织中的表达并探讨其表达与结肠癌临床病理特征的关系.方法 收集2011年3月至9月襄阳市中心医院手术切除的原发性结肠癌标本57例,分别提取结肠癌和正常黏膜组织中总RNA并行逆转录反应,应用实时荧光逆转录聚合酶链反应检测肿瘤组织及正常黏膜组织中miR-155的表达水平,探讨其表达与结肠癌临床病理参数间的关系.配对标本采用非参数Wilcoxon秩和检验,两独立样本采用u检验.结果 miR-155在结肠癌组织中相对表达水平为0.421(0.016 ～1.241),显著高于其在正常黏膜组织中表达的0.128(0.000～0.337),两者比较,差异有统计学意义(u=3.783,P＜0.05);miR-155的表达增高与TNM分期、肿瘤浸润程度、淋巴结转移、肿瘤分化程度明显相关(u=2.364,2.152,2.338,2.214,P＜0.05).结论 miR-155在结肠癌组织中表达增高,miR-155可能作为原癌基因参与结肠癌的发生、发展,与结肠癌的侵袭、转移密切相关.     

miR-27在乳腺癌中的表达及意义

目的 检测乳腺癌组织中miR-27的表达,并探讨其表达水平与乳腺癌临床病理特征的相关性。方法 采用原位杂交技术检测67例乳腺癌组织中miR-27的表达,分析其表达水平在复发转移组并与无复发转移组的差异与肿瘤大小、淋巴结转移、雌激素受体(ER)、孕激素受体(PR)、HER-2及月经状况等临床病理特征之间的关系。结果 miR-27在转移组乳腺癌组织中的表达明显高于非转移组（P ＜0.01 );miR-27的表达与肿瘤的大小有关（P ＜0.05）,与淋巴结转移有关（P ＜0.01 );与雌孕激素受体、Her2及月经状况未见明显的统计学差异（P ＞0.05）。结论 miR-27在乳腺癌组织中高表达可能与乳腺癌的恶性程度及预后有关,有可能成为乳腺癌新的预后指标及治疗靶点。     

PCOS患者血清miR-320a、miR-145表达水平及其与雌孕激素的关系探讨

目的 探讨多囊卵巢综合征(PCOS)患者血清微小RNA-320a(miR-320a)、miR-145表达水平及其与雌、孕激素的关系。方法 采用前瞻性研究,选取2019年5月至2021年7月于本院就诊的92例PCOS患者作为PCOS组,另招募同期健康体检的90例育龄期女性作为对照组。采用实时荧光定量PCR(Real-time PCR)法检测并比较两组患者血清miR-320a和miR-145表达水平,采用电化学发光法检测并比较两组患者血清E₂和孕酮水平;采用Pearson相关性分析探讨PCOS患者血清miR-320a、miR-145表达水平与雌孕激素的关系。结果 电化学发光检测结果显示,PCOS组血清E₂和孕酮水平显著低于对照组(P<0.05);Real-time PCR检测结果显示,PCOS组血清miR-320a和miR-145表达水平均显著低于对照组(P<0.05);Pearson相关性分析结果显示,PCOS组血清miR-320a和miR-145表达水平与E₂和孕酮水平均呈显著正相关(P<0.05)。结...     

膀胱癌患者尿液中miR-126、miR-152的表达水平及临床意义

目的 研究miR-126与miR-152在膀胱癌患者尿液中的表达,评估二者作为膀胱癌早期诊断标志物的价值. 方法 采用RT-PCR技术检测52例膀胱癌患者和40例健康对照者尿液中miR-126、miR-152的表达,并通过受试者工作曲线(ROC)分析其诊断效能. 结果 miR-126在早期膀胱癌患者尿液中表达显著升高(t=6.350,P＜0.01),且与膀胱癌的恶性程度有关;膀胱癌患者尿液中miR-152表达降低(t=3.996,P＜0.05),但与膀胱癌的临床病理特征均无关(P＞0.05);miR-126联合miR-152能够很好地鉴别膀胱癌,敏感性和特异性分别为76.5％、83.6％.结论 尿液中的miR-126能够反映膀胱癌的恶性程度,miR-126联合miR-152对膀胱癌的早期诊断具有潜在的价值.     

乳腺癌组织中 miR-21的表达及意义

目的 对乳腺癌组织及其相应癌旁组织中miR-21进行定量检测,分析其表达与临床病理特征的及意义.方法 采用茎环实时荧光逆转录聚合酶链反应(RT-PCR)检测60例乳腺癌及其对应癌旁组织中miR-21的表达量,分析其表达与肿瘤大小、TNM分期、组织学类型、淋巴结转移、雌激素受体(ER)、孕激素受体(PR)等临床病理特征的关系.结果 实时RT-PCR方法 检测miR-21表达的敏感性和特异性良好.miR-21在乳腺癌组织中的表达明显高于癌旁组织(P＜0.001);miR-21的高表达还与较高的TNM分期,淋巴结转移及PR的表达程度有关(各分组间P＜0.01及＜0.05);miR-21的表达在"三阴性乳腺癌"(ER,PR,CerbB-2均为阴性)和"非三阴性乳腺癌"之间的表达存在统计学差异(P=0.029).结论 miR-21在乳腺癌组织中高表达,其水平可能与乳腺癌的恶性程度有关.     

miR-34a在膀胱癌中下调MTA2表达的研究

目的 研究微小核糖核酸34a（microRNA-34a,miR-34a）在膀胱癌中的表达及临床意义,确定转移相关基因2（metastasis-associated gene2,MTA2）是否为miR-34a调控的下游靶基因,探讨膀胱癌中miR-34a与MTA2的相互作用机制。方法 选取48对膀胱癌根治术后癌组织及癌旁组织,标本来源于2011年5月至2012年5月我科收治的膀胱癌患者。Real-time PCR检测miR-34a和MTA2在组织中RNA的表达情况;荧光素酶实验鉴定MTA2是否为miR-34a下游靶基因;膀胱癌细胞株T24及UMUC3中转入miR-34a后,琼脂糖凝胶电泳、免疫印迹实验检测MTA2的RNA及蛋白表达。结果 Real-time PCR检测表明,膀胱癌组织中miR-34a呈低表达,并且与肿瘤分期有关（P〈0.01）;MTA2在癌组织中表达明显上调。MiRanda、Mirwalk、Targetscan软件预测miR-34a与MTA2的mRNA有结合位点,荧光素酶实验结果表明MTA2可能是miR-34a的潜在靶基因。转染miR-34a后,分别检测MTA2的蛋白和mRNA表达情况,发现MTA2蛋白受到抑制,mRNA表达不受影响。结论 miR-34a在膀胱癌中可能通过作用于其潜在靶基因MTA2而发挥抑癌基因作用。     

Glomerular and tubulointerstitial miR-638, miR-198 and miR-146a expression in lupus nephritis

Aim: MicroRNAs (miRNAs) play important roles in the pathogenesis of autoimmune diseases. We studied the intra‐renal expression of miRNA targets that were reported to be differentially expressed in peripheral blood or urine between lupus nephritis (LN) patients and normal controls. Methods: We quantified the expression of in glomerulus and tubulointerstitium of miR‐146a, miR‐155, miR‐198 miR‐638 and miR‐663 in 42 patients with LN and 10 healthy controls. Results: As compared with controls, LN patients had lower glomerular expression of miR‐638 (P < 0.001) but higher tubulointerstitial expression of this target (P = 0.001). Both glomerular and tubulointerstitial expression of miR‐198 were higher in LN patients than controls (P < 0.001). For miR‐146a, LN patients only had higher expression in glomerulus (P = 0.005) but not in tubulointerstitium. Tubulointerstitial miR‐638 expression was significantly correlated with proteinuria (r = 0.404; P = 0.022) and disease activity score (r = 0.454; P = 0.008), while glomerular miR‐146a expressions were correlated with estimated GFR (r = 0.453; P = 0.028) and histological activity index (r = 0.494; P = 0.027). Conclusion: We found that intra‐renal expression of miR‐638, miR‐198 and miR‐146a are differentially expressed between LN patients and normal controls. Furthermore, the degree of change in glomerular miR‐146a and tubulointerstitial miR‐638 expression correlated with clinical disease severity. The results suggested that these miRNA targets may play a role in the pathogenesis of lupus nephritis.     

miR-21, miR-221 and miR-222 expression and prostate cancer recurrence among obese and non-obese cases

Recent evidence shows that certain microRNAs (miRNAs) play a role in both obesity and prostate cancer recurrence, but the association between the expression of these miRNAs and obesity in prostate cancer recurrence is unknown. In this study, we examined the effect of the interaction between obesity and miR-21, miR-221 or miR-222 expression on prostate cancer recurrence among 28 recurrent and 37 non-recurrent prostate cancer cases. miRNA expression was determined using quantitative real-time polymerase chain reaction. Cox proportional hazard models adjusting for age at diagnosis, clinical stage and Gleason score were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for recurrence free survival. A significantly (P=0.014) higher proportion of recurrent cases (78.6%) than non-recurrent cases (48.6%) had a low expression of miR-21 and the difference was more prominent in obese than non-obese patients. Multivariate analysis showed that the expression of miR-21 was an independent risk factor for recurrence in obese (HR=6.15, 95% CI=1.04–36.48, P=0.045), but not in non-obese (HR=1.28, 95% CI=0.30–5.49, P=0.74) cases. A significant association with recurrence was not observed for the expression of miR-221 and miR-222. In summary, our findings show that miR-21 is associated with prostate cancer recurrence after radical prostatectomy and suggest that the differential expression of miR-21 is more prominent in obese than in non-obese cases. Future larger studies are warranted to confirm these initial findings and to elucidate the mechanisms involved.     

miR-150 和miR-134 在结直肠癌及腺瘤中的表达

目的：探讨miR-150和miR-134在结直肠癌与结直肠腺瘤中的表达及意义。 方法：采用实时定量荧光PCR（qRT-PCR）检测40例结直肠癌组织及其癌旁正常组织与29例结直肠腺瘤组织中miR-150和miR-134表达,并分析两者与结直肠癌临床病理因素之间的关系。 结果：与癌旁正常组织比较,miR-150在腺瘤组织中表达明显升高,而在癌组织中表达明显降低（均P<0.05）;miR-134在腺瘤组织中表达明显降低（P<0.05）,但在癌组织中表达差异无统计学意义（P>0.05）;miR-150表达水平与结直肠癌的组织学类型及分化程度有关（P=0.033,P=0.041）;miR-134表达水平与结直肠癌的各项临床病理因素均无明显关系（均P>0.05）。 结论：miR-150在结直肠癌中表达下调,提示其可能有潜在的抑癌作用,miR-150和miR-134在结直肠腺瘤中的表达均发生异常,提示两者均可能与结直肠腺瘤的发生密切相关。     

miR-16和miR-302在乳腺癌组织中的表达及临床意义

探究微小RNA-16(miR-16)、微小RNA-302(miR-302)在乳腺癌组织中的表达及其临床意义.2016年1月—2017年3月,经手术切除且经病理证实的乳腺癌组织标本40例,癌旁正常组织40例.采用实时荧光定量PCR(qRT-PCR)检测乳腺癌组织及癌旁正常组织中miR-16、miR-302表达水平;采用K...     

miR-143和miR-145在胃癌中的表达及功能研究

目的：探讨miR-143和miR-145在胃癌组织中的表达情况,观察其生物学功能。方法通过高通量芯片检测比较11对胃癌原发灶及其配对肝转移灶的miRNA表达谱,采用Real-time PCR方法观察miR-145和miR-143在55例胃癌组织中的表达情况。同时使用Transwell方法观察其对细胞转移能力的影响。结果 miR-143和miR-145在胃癌组织中的表达明显低于癌旁正常组织（miR-143：0．028±0．005比0．052±0．014,P＝0．058;miR-145：0．922±0．135比1．772±0．285,P＝0．007）,在转移灶中的表达明显低于原发灶（miR-143：0．059±0．025比0．182±0．045,P＝0．021;miR-145：0．164±0．076比0．594±0．283,P＝0．042）,相关性分析显示,miR-143和miR-145表达具有显著相关性（r＝0．400, P＝0．000）。体外实验显示,两者可协同抑制胃癌细胞系转移。结论 miR-145和miR-143可能参与胃癌转移进程,并且两者可能发挥协同作用。     

miR-214和miR-181c在胃癌组织中的表达及预后价值

目的探讨微小RNA-214（miR-214）和miR-181c在胃癌组织中的表达水平及对预后的影响。 方法选取2014年1月至2015年1月于川北医学院附属医院收治的68例胃癌患者为研究对象,均接受手术治疗,出院后随访1~60个月。利用实时荧光定量PCR技术检测患者癌组织和癌旁组织miR-214、miR-181c相对表达量;利用Kaplan-Meier曲线进行生存分析;Cox多因素回归分析影响胃癌患者预后的独立危险因素。 结果胃癌组织中miR-214、miR-181c表达水平均明显低于癌旁组织,差异有统计学意义（P<0.05）。根据miR-214、miR-181c表达均值将患者分为高表达组和低表达组,miR-214、miR-181c表达水平与年龄、性别、淋巴结是否转移无关,与TNM分期、肿瘤分化程度有关（P<0.05）。患者总生存率为44.12%,miR-214低表达组和高表达组术后5年累积生存率分别为35.71%、57.69%,两组间比较差异有统计学意义（P=0.035）;miR-181c低表达组和高表达组术后5年累积生存率分别为35.55%、60.87%,差异有统计学意义（P=0.024）。Cox多因素回归分析结果显示,TNM分期高（HR=1.569,95% CI：1.029~2.391,P=0.036）、miR-214低表达（HR=1.643,95% CI：1.294~2.087,P<0.001）及miR-181c低表达（HR=1.327,95% CI：1.045~1.685,P=0.021）是影响胃癌患者预后的独立危险因素。 结论miR-214、miR-181c在胃癌组织中表达显著下调,与胃癌患者临床病理参数及不良预后有关,参与胃癌的发生发展过程。     

Sperm miR-15a and miR-29b are associated with bull fertility

MicroRNAs modulate male fertility by regulating gene expression. In this study, dynamics of sperm miR-15a, miR-29b and miR-34a from high fertility (HF) and low fertility (LF) bulls using RT-qPCR were evaluated. Bioinformatic tools were employed to ascertain genes of interest of the sperm miRNAs. The expression levels of p53, BCL2, BAX and DNMT1 in bull spermatozoa were determined by immunoblotting. MicroRNA levels of miR-15a and miR-29 were higher in LF sires when compared with those present in HF bulls. Expression levels of miR-34a did not differ between the two groups. We found an inverse correlation between miR-15a and bull fertility. MiR29-b was also negatively associated with fertility scores. BCL2 and DNMT1 were higher in HF bulls while BAX was higher in the LF group. Our data showed a positive correlation between BCL2 and bull fertility. In addition, DNMT1 was positively associated with bull fertility. Furthermore, levels of BAX were negatively linked with bull fertility scores. Identification of miRNAs found in the spermatozoa of sires with different in vivo fertility helps understand the alterations in the fertilising capacity from cattle and other mammals. These potential biomarkers can be used in reproductive biotechnology as fertility markers to assess semen quality and predict male fertility.     

miR-335 and miR-34a Promote renal senescence by suppressing mitochondrial antioxidative enzymes

The molecular basis for aging of the kidney is not well understood. MicroRNAs (miRNAs) contribute to processes such as development, differentiation, and apoptosis, but their contribution to the aging process is unknown. Here, we analyzed the miRNA expression profile of young (3-month) and old (24-month) rat kidneys and identified the biologic pathways and genes regulated by differentially expressed miRNAs. We observed upregulation of 18 miRNAs with aging, mainly regulating the genes associated with energy metabolism, cell proliferation, antioxidative defense, and extracellular matrix degradation; in contrast, we observed downregulation of 7 miRNAs with aging, principally targeting the genes associated with the immune inflammatory response and cell-cycle arrest. Bioinformatics analysis suggested that superoxide dismutase 2 (SOD2) and thioredoxin reductase 2 (Txnrd2), located in the mitochondria, are potential targets of miR-335 and miR-34a, respectively. Aging mesangial cells exhibited significant upregulation of miR-335 and miR-34a and marked downregulation of SOD2 and Txnrd2. miR-335 and miR-34a inhibited expression of SOD2 and Txnrd2 by binding to the 3'-untranslated regions of each gene, respectively. Overexpression of miR-335 and miR-34a induced premature senescence of young mesangial cells via suppression of SOD2 and Txnrd2 with a concomitant increase in reactive oxygen species (ROS). Conversely, antisense miR-335 and miR-34a inhibited senescence of old mesangial cells via upregulation of SOD2 and Txnrd2 with a concomitant decrease in ROS. In conclusion, these results suggest that miRNAs may contribute to renal aging by inhibiting intracellular pathways such as those involving the mitochondrial antioxidative enzymes SOD2 and Txnrd2.