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1.
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.  相似文献   

2.
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.  相似文献   

3.
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。  相似文献   

4.
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...  相似文献   

5.
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.  相似文献   

6.
目的检测肾移植受者术后血浆外泌体miR-21、miR-210和miR-4639表达变化,分析外泌体miR-21、miR-210和miR-4639单独及联合对肾移植术后并发慢性移植肾肾病(CAN)的诊断价值。 方法回顾性分析2018年1月至2019年1月苏州大学附属第三医院泌尿外科实施的同种异体肾移植受者临床资料,最终纳入34例受者,根据肾移植术后是否发生CAN将其分为CAN组及对照组。采用凝胶排阻色谱法提取血浆外泌体,采用Nanosight NS300分析外泌体粒径,采用蛋白质印迹法(WB)分析外泌体表面标志物(CD63和Alix)表达情况。采用卡方检验比较CAN组和对照组受者性别比例。采用成组t检验比较两组受者移植前年龄、末次血清肌酐、血清尿素氮和估算肾小球滤过率(eGFR)。采用受试者工作特征(ROC)曲线评价血浆外泌体miR-210、miR-21和miR-4639对肾移植术后并发CAN的诊断效能。P<0.05为差异有统计学意义。 结果CAN组(n=18例)和对照组(n=16例)受者性别以及移植前年龄、末次血清肌酐、血清尿素氮和eGFR差异均无统计学意义(χ2=0.04、t=0.86、-1.84、-1.83和0.85,P均>0.05)。透射电镜、Nanosight NS300及WB检测结果均提示提取样本为血浆外泌体。CAN组与对照组血浆外泌体miR-210、miR-21和miR-4639相对表达量差异均有统计学意义(t=4.13、3.38和2.33,P均<0.05)。miR-210预测肾移植术后并发CAN的ROC曲线下面积为0.854(95%CI:0.730~0.979,P<0.05),当截断值=1.320时,敏感度为66.7%,特异度为93.8%。miR-21预测肾移植术后并发CAN的ROC曲线下面积为0.774(95%CI:0.618~0.931,P<0.05),当截断值=1.243时,敏感度为55.6%,特异度为93.8%。miR-4639预测肾移植术后并发CAN的ROC曲线下面积为0.670(95%CI:0.482~0.859,P<0.05),当截断值=0.936,敏感度为66.7%,特异度为75.0%。随后,构建基于miR-210、miR-21和miR-4639 3个指标的联合诊断模型,回归方程z=5.293×[miR-210]+5.046×[miR-21]+0.433×[miR-4639]-13.373,联合预测概率值p=ez/(1+ez)。miR-210、miR-21和miR-4639联合预测肾移植术后并发CAN的ROC曲线下面积为0.938(95%CI:0.860~1.015,P<0.05),当截断值=0.587,敏感度为83.33%,特异度为93.75%。当联合预测值为0.587时,CAN组有83.3%(15/18)的个体被联合预测模型诊断出阳性结果,而对照组有93.8%(15/16)的个体被联合预测模型诊断出阴性结果,表明该联合预测模型有较好的诊断价值。 结论miR-210、miR-21和miR-4639组成的miRNA阵列可能可以用于早期诊断肾移植术后并发CAN。  相似文献   

7.
8.

Purpose

Prostate cancer (PCa) is a common tumor disease in western countries and a leading cause of cancer-driven mortality in men. Current methods for prostate cancer detection, like prostate-specific antigen screening, lead to significant overtreatment. The purpose of the study was to analyze circulating microRNAs in serum as non-invasive biomarkers in patients with diagnosis of prostate cancer and healthy individuals.

Methods

This preliminary study included a population of 20 patients with mean age of 68.6 years and mean PSA of 21.3 ng/ml. Eight healthy patients were used as control. MiRNAs were quantified in the total RNA fraction extracted from serum and levels of five microRNAs (miR-106b, miR-141, miR-21, mir-34a, and miR-375) were quantified by RT-qPCR. Statistical analyses evaluated correlation between clinicopathological data and miRNAs expression levels.

Results

Relative expression ratios of miR-106b, miR-141-3p, miR-21, and miR-375 were significantly increased (1.8-, ?1.9-, 2.4-, and 2.6-fold, respectively) in the PCa group compared to healthy control. Using receiver operating characteristics, the highest area under the curve equal to 0.906 was obtained for miR-357 and indicates a very good diagnostic properties of this biomarker. We found expression level of mir-34a not related with PCa.

Conclusions

Our results support previous findings on the possibility of discriminating prostate cancer patients from healthy controls by detecting miRNA (miR-141-3p, miR-21, and miR-375). Further insights into miRNA abundance and characteristics are necessary to validate the panel of miRNA as surrogate markers in diagnosis of prostate cancer.
  相似文献   

9.
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.  相似文献   

10.
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。  相似文献   

11.
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。  相似文献   

12.
miR-143和miR-145在胃间质瘤组织中的表达及其意义   总被引:1,自引:0,他引:1  
目的 探讨miR-143和miR-145在胃间质瘤发生发展中的作用.方法 采用茎环即时RT-PCR方法检测21例胃间质瘤及其正常胃组织中miR-143和miR-145的表达,分析其与临床病理因素的关系.结果 本组胃间质瘤组织中miR-145表达显著高于正常胃组织(P<0.01),且核分裂数≥5/50 HPF病例的miR-145表达显著低于核分裂数<5/50 HPF病例(P=0.02),巨大肿瘤(直径>10 cm)的miR-145表达显著低于大肿瘤(5~10 cm)病例及小肿瘤(2~5 cm)病例(P=0.048),Fletcher分级高危病例的miR-145表达显著低于中危及低危分级病例(P=0.048),低危组与中、高危组miR-145表达相比差异有统计学意义(P=0.01).胃间质瘤组织中miR-143表达与正常胃组织相比差异无统计学意义(P=0.06). 结论 miR-145在胃间质瘤组织中表达上调,且与肿瘤大小、核分裂象及Fletcher分级等密切相关,提示其在胃间质瘤的发生发展过程中发挥重要作用.  相似文献   

13.
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.  相似文献   

14.
目的检测miR-218和miR-152在浆液性卵巢癌中的表达情况,并探讨其临床意义。方法取正常输卵管伞端上皮组织、良性病变卵巢组织以及浆液性卵巢癌组织,应用Real-time PCR技术检测miR-218和miR-152在上述组织中的表达情况,分析其表达与卵巢癌临床病理特征之间的关系。结果 Real-time PCR检测显示,卵巢癌组织中miR-218和miR-152的表达(分别为404.5和382.9)显著低于正常输卵管伞端上皮组织(分别为598.7和678.4)和良性病变组织(分别为523.3和587.3)(P0.05);miR-218的低表达与卵巢癌恶性程度、肿瘤分化程度以及肿瘤转移情况相关(P0.05),而miR-152的表达与浆液性卵巢癌各临床病理特征无显著相关性(P0.05)。结论 miR-218和miR-152在浆液性卵巢癌组织中低表达,miR-218有可能成为浆液性卵巢癌诊断和预后的标志物。  相似文献   

15.
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.  相似文献   

16.
目的探讨微小RNA-21(miR-21)和miR-17-5p在乳腺癌患者血浆外泌体中的表达水平及其诊断价值。 方法选取2017年6月至2018年3月于成都市第七人民医院就诊的86例乳腺癌患者为乳腺癌组,选取同期体检健康女性45例为对照组。采用实时定量聚合酶链反应(qRT-PCR)检测miR-21、miR-17-5p在两组血浆外泌体中的表达水平。根据qRT-PCR检测结果将乳腺癌患者分为miR-17-5p高表达组及低表达组,miR-21高表达组及低表达组,比较分析其与乳腺癌患者临床病理参数的关系。采用受试者工作特征曲线(ROC)分析血浆外泌体miR-21、miR-17-5p对乳腺癌的诊断价值。 结果乳腺癌组患者血浆外泌体miR-17-5p表达水平显著低于对照组(P<0.05),而miR-21表达水平显著高于对照组(P<0.05);miR-17-5p单独检测时曲线下面积(AUC)为0.677,敏感度为58.14%,特异度为75.56%,截断值为0.72;miR-21单独检测时AUC为0.694,敏感度为59.30%,特异度为77.78%,截断值为1.68;联合检测时敏感度为96.51%,特异度为95.56%,准确性为96.18%;联合检测诊断乳腺癌的敏感度、特异度及准确性均显著高于单项检测(P<0.05)。血浆外泌体miR-17-5p、miR-21表达水平均与TNM分期、分化程度、淋巴结转移、cerbB-2及Ki-67有关(P<0.05)。 结论血浆外泌体低表达的miR-17-5p与高表达的miR-21均可作为诊断乳腺癌的潜在生物学标志物。  相似文献   

17.
Carcinogenesis is a complex process during which cells undergo genetic and epigenetic alterations. These changes can lead tumor cells to acquire characteristics that enable movement from the primary site of origin when conditions become unfavorable. Such characteristics include gain of front-rear polarity, increased migration/invasion, and resistance to anoikis, which facilitate tumor survival during metastasis. An epithelial to mesenchymal transition (EMT) constitutes one way that cancer cells can gain traits that promote tumor progression and metastasis. Two microRNA (miRNA) families, the miR-200 and miR-221 families, play crucial opposing roles that affect the differentiation state of breast cancers. These two families are differentially expressed between the luminal A subtype of breast cancer as compared to the less well-differentiated triple negative breast cancers (TNBCs) that exhibit markers indicative of an EMT. The miR-200 family promotes a well-differentiated epithelial phenotype, while high miR-221/222 results in a poorly differentiated, mesenchymal-like phenotype. This review focuses on the mechanisms (specific proven targets) by which these two miRNA families exert opposing effects on cellular plasticity during breast tumorigenesis and metastasis.  相似文献   

18.
目的 分析人直肠癌组织miR-155和miR-200c的表达差异及其与直肠癌临床病理特征的关系.方法 选取手术切除的卣肠癌标本71例,以正常黏膜为对照,采用实时荧光定量-聚合酶链反应(qRT-PCR)对miR-155和miR-200c作定量分析.结果 相对于正常黏膜组织,miR-155和miR-200c在直肠癌组织中表达上调,差异有统计学意义(P<0.05).miR-155的表达与患者年龄有关(P<0.05);miR-200c的表达与患者血清癌胚抗原(CEA)水平有关(P<0.05).不同的直肠癌性别、临床分期、浸润深度、淋巴结转移、远处转移和分化程度间miR-155、miR-200c表达的差异无统计学意义(P>0.05).结论 miR-155和miR-200c在直肠癌组织中显著表达,可能参与直肠癌的发生过程.miR-200c对于直肠癌町能具有潜在的辅助诊断、疗效判断及预后评估意义.  相似文献   

19.
Background  Genetic and epigenetic alterations during development of pancreatic ductal adenocarcinomas (PDAC) are well known. Genetic and epigenetic data were correlated with tumor biology to find specific alterations responsible for invasion and metastasis in pancreatic ductal adenocarcinomas. Methods  A total of 16 human PDAC cell lines were used in murine orthotopic PDAC models. By means of standardized dissemination scores, local invasion and metastatic spread were assessed. mRNA and microRNA expression were studied by microarray and TaqMan low-density array. Quantitative real-time–polymerase chain reaction and flow cytometry were used for expression validation. Results   CD40 was detected as a relevant target gene for differentially expressed miRNAs observed in highly invasive and metastatic PDAC only. A significant overexpression (P < .05) of CD40-related miRNAs miR-224 and miR-486 was detected in highly invasive and metastatic PDAC, whereas CD40 mRNA expression was not significantly altered. Instead, CD40 protein expression at cell surfaces of these highly invasive and metastatic PDAC was significantly reduced (P < .01). Conclusions  Epigenetic alterations with upregulated CD40-targeting miR-224 and miR-486 are related to downregulated CD40 protein expression at cell surfaces in highly invasive and metastatic PDAC. Thus, miRNA-regulated CD40 expression seems to play an important role in progression of PDAC. These data suggest a diagnostic and therapeutic potential for CD40 and/or its targeting miRNAs in PDAC.  相似文献   

20.
目的:探究结肠癌组织中微小RNA(miR)-192和miR-23a水平变化及其临床意义。方法:收集2009年3月—2012年10月我院手术切除并经病理学检查确诊的结肠癌标本71例及肠息肉标本45例,采用原位杂交法检测结肠癌组织及肠息肉组织中miR-192和miR-23a水平,分析结肠癌组织中miR-192和miR-23a水平与临床病理特征的关系。选用结肠癌SW620细胞系作为研究对象,分为对照组、miR-192组及miR-23a组,其中对照组不作处理,miR-192组及miR-23a组细胞分别进行miR-192及miR-23a转染,采用Transwell实验检测3组结肠癌细胞的侵袭能力。结果:结肠癌组织中miR-192水平明显低于肠息肉组织(P<0.05),miR-23a水平明显高于肠息肉组织(P<0.05);miR-192及miR-23a水平与结肠癌浸润深度、淋巴结转移情况及Dukes分期有关(P<0.05);结肠癌组织中miR-192表达水平与miR-23a表达水平呈负相关(r=-0.805,P<0.05)。miR-192组结肠癌细胞相同时间内穿过小室数明显低于对照组及miR-23a组,miR-23a组结肠癌细胞相同时间内穿过小室数明显高于对照组(P<0.05)。结论:结肠癌组织中miR-192水平下降,miR-23a水平上调;miR-192和miR-23a表达水平与浸润深度、淋巴结转移情况及Dukes分期有关;结肠癌组织中miR-192和miR-23a水平呈负相关;miR-192抑制结肠癌细胞侵袭能力,miR-23a能增强结肠癌细胞侵袭能力。  相似文献   

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