microRNAs在胃癌发生发展中的研究进展

微小RNAs（miRNAs）是一组小的非编码RNA,在胃癌中起着至关重要的作用。miRNAs通过靶基因mRNA产生双重的、相反的作用,即致癌或抑癌作用。致癌miRNAs在胃癌中过表达,并能抑制肿瘤抑制基因。相反,肿瘤抑制miRNAs在胃癌中表达通常下调,从而导致癌症的发展。异常表达的miRNAs参与胃癌的发生发展并调控不同的表型,如增殖、凋亡、转移及耐药性等。此外,miRNAs还可用于胃癌的诊断和预后预测等。本文综述了miRNAs在胃癌发展中的作用,以及miRNAs在诊断和预后中的潜在应用价值。     

MicroRNAs相关的胃癌研究进展

MicroRNAs（miRNAs）是一类广泛存在于真核细胞中长22-25nt的单链、非蛋白编码RNA,具有转录后基因调控的功能,调节细胞增殖、凋亡以及分化等多种生物学过程。近年来研究发现,miRNAs与胃癌的发生、发展关系密切。本文就与胃癌相关的miRNAs及其在肿瘤发生、发展中的研究进展作一综述。     

血清外泌体miRNAs联合CA72-4在胃癌诊断中的价值分析

  目的  筛选胃癌患者及健康人血清外泌体miRNAs,探究miRNAs联合肿瘤标记物在胃癌诊断中的价值。  方法  选取2020年4月至2021年4月在苏州大学附属第一医院确诊胃癌的46例患者为胃癌组,同期20例健康体检者为对照组,收集两组血清标本,行血清外泌体miRNAs测序,筛选并验证差异性表达的miRNAs,将验证后的miRNAs表达水平、肿瘤标志物数值与胃癌诊断行Spearman相关分析,并绘制受试者工作特征（receiver operating characteristic ,ROC）曲线,分别分析外泌体miRNAs、CA72-4及两者联合在胃癌诊断中的价值。  结果  两组血清外泌体共筛选出376个差异表达的miRNAs,经q-PCR验证,仅4个miRNAs差异具有统计学意义,采用ROC曲线判断外泌体miRNAs在胃癌诊断中的效能:miR-1323、miR-26a-5p、miR-202-3p、miR-96-5p诊断胃癌的曲线下面积（area under curve,AUC）分别为0.908、0.815、0.570、0.547,灵敏度分别为71.7%、67.4%、30.4%、19.6%,特异度分别100%、85.0%、90.0%、100%。Spearman相关分析结果提示:miR-26a-5p、miR-1323和CA72-4与胃癌诊断相关,ROC曲线显示:miR-26a-5p、miR-1323和CA72-4三者联合诊断的曲线下面积为0.967,高于三者单独诊断效能,其灵敏度和特异度分别为87.0%、100%。  结论  联合检测血清外泌体miR-26a-5p、miR-1323和CA72-4的表达水平,在胃癌诊断中具有潜在价值。      

MicroRNAs在胃癌中的研究进展

MicroRNAs(miRNAs)是长度约22个核苷酸片段的进化保守分子,其转录后通过沉默目的基因而调节基因表达.miRNAs参与几乎所有的生物学过程,如增殖、凋亡、细胞分化/代谢、上皮间质细胞转化等等,且与肿瘤发生密切相关.miRNAs作用取决于其目的基因.miRNAs一旦功能失调,它们调节细胞生长、细胞周期、细胞迁移的作用即变为抑癌或致癌.由于缺乏高度敏感非侵入性诊断标志物,胃癌高危个体的早期诊断率和总生存率仍然很低.近期许多研究表明,miRNAs是一个很有前景的生物学标志物,可以决定胃癌患者预后并预测生存期和胃癌患者复发.文章主要就microRNAs作为新兴生物学标志物在胃癌的研究进展作一综述.     

胃癌miRNAs表达谱及胃癌组织miR-21表达临床意义探讨

目的:筛选胃癌miRNAs表达谱,探讨miR-21在胃癌组织中的表达情况及其临床病理意义.方法:收集手术切除新鲜胃癌标本共65例,包括胃癌组织及相应胃正常上皮组织,随机选取其中6例,应用miRNA芯片技术研究胃癌的miRNAs表达谱.采用实时定量PCR验证芯片结果并检测miR-21在65例胃癌组织标本及相应胃正常上皮组织的表达水平,探讨其表达与胃癌临床病理参数间的关系.结果:与胃正常上皮组织相比,胃癌组织中表达上调超过2倍的miRNAs有7个(miR-374b*、miRPlus-E1212、miR-338-5p、miR-297、miR-21、miR-135b和miR-18a),表达下调超过2倍的miRNAs有9个(miR-29b-2*、miR-1260、miRPlus-E1241、miR-S1-5p、miR-148a、miR-29c、miR-647、miR-196b×和ebv-miR-BART5).46例(70.8％)胃癌组织中miR-21表达水平明显高于胃正常上皮组织,且与肿瘤的分化程度(x2=6.257,P=0.012)、浸润深度(x =5.705,P=0.017)和有无淋巴结转移(x2=7.107,P=0.008)有关.结论:筛选出的差异表达miRNAs可能参与胃癌的发病;miR-21与胃癌生物学行为密切相关,可能成为胃癌诊断和治疗的潜在生物学指标.     

胃癌发生过程中风险miRNAs筛选及其诊断效能评价的多中心研究

目的 探索胃癌发生过程的风险miRNAs,为上消化道机会性筛查中早期胃癌识别提供依据。方法 纳入2021年6月至2023年8月在广西医科大学附属肿瘤医院、右江民族医学院附属医院、桂林市人民医院3个中心进行上消化道癌机会性筛查的人群。选取健康体检者107例、早期胃癌患者71例、进展期胃癌患者97例。首先采用转录组测序筛选差异表达miRNAs,然后在3组前瞻性人群的血浆样本中通过RT-qPCR验证差异表达的miRNAs,最后采用受试者工作特征（receiver operating characteristic,ROC）曲线评估miRNAs的诊断效能。结果 转录组测序的差异基因分析共筛选出胃癌发生过程中的6个差异表达miRNAs,包括miR-3176、miR-885-5p、miR-203a-3p、miR-452-5p、miR-223-3p、miR-219a-2-3p。RT-qPCR结果显示,miR-452-5p在早期胃癌及进展期胃癌患者中表达上调（均P<0.001）。ROC曲线显示,miR-452-5p诊断早期胃癌和进展期胃癌的曲线下面积（area under the curve,AU...     

靶向PIK3CA候选miRNAs在胃癌细胞与血清中表达的分析

目的:预测和筛选靶向PIK3CA的候选miRNAs并检测其在胃癌细胞和血清中的表达.方法:采用生物信息学并结合既往文献和前期研究,预测和筛选出靶向PIK3CA的候选miRNAs(miR-203和miR-506).常规提取胃癌细胞和血清总RNA,并用DNase Ⅰ进行消化.以miRNAs特异性茎-环引物引导反转录,通过实时荧光定量PCR对miR-203、miR-506和内参U6进行检测,并采用琼脂糖凝胶电泳检测定量PCR产物.结果:电泳检测细胞和血清中RNA纯度较好；胃癌细胞和血清中miR-203、miR-506和内参U6均能实现特异性扩增.miR-203在胃癌细胞SGC-7901及MGC-803中表达分别为1.360±0.102和1.241±0.110,差异无统计学意义,t=3.125,P=0.09;miR-203在胃癌患者血清中表达为1.420±0.122,明显低于健康人的3.450--0.206,t=2.521,P=0.02.miR-506在胃癌细胞SGC-7901和MGC-803及胃癌患者和健康人血清中表达水平分别为1.256±0.113、1.158±0.109、1.735±0.220和1.592±0.134,差异无统计学意义,P＞0.05.结论:miR-203可能是调控PIK3CA基因的miRNAs之一.PIK3CA在胃癌中的高表达可能与miR-203的异常低表达有关,而与miR-506无关.胃癌患者血清中miR-203的表达有望成为预测胃癌发生或发展的一个重要的分子标志.     

血清外泌体miRNAs在晚期胃癌患者化疗疗效预测中的价值

  目的  通过筛选晚期胃癌患者血清外泌体miRNAs，探讨外泌体miRNAs在化疗疗效预测中的价值。  方法  收集苏州大学附属第一医院2018年4月至2020年11月确诊为初治Ⅳ期胃腺癌患者36例病例资料，均接受不少于2个周期的Xelox或SOX方案化疗，根据实体肿瘤疗效评价标准（RECIST标准）分为敏感组和耐药组，收集患者首次化疗前的血清标本，提取血清外泌体RNA，行miRNAs测序，筛选出差异表达显著的miRNAs，并采用实时荧光定量PCR对筛选的miRNAs进行验证，使用受试者工作特征曲线（receiver operating characteristic curve，ROC），判断验证后的外泌体miRNAs在疗效预测中的价值。  结果  36例Ⅳ期胃癌患者按照RECIST标准，分为敏感组15例，耐药组21例。两组患者血清外泌体中共筛选出527个差异表达的miRNAs，经qRT-PCR验证后，仅3个外泌体miRNAs差异具有统计学意义，ROC曲线预测miRNA-106a-5p、miRNA-1323、miRNA-202-3p与胃癌化疗疗效的曲线下面积分别为0.952、0.949、0.946，灵敏度分别为90.5%、90.1%、85.7%，特异度分别为:93.3%、86.7%、93.1%。  结论  检测晚期胃癌患者血清外泌体miRNA-106a-5p、miRNA-1323、miRNA-202-3p，可能对化疗疗效具有一定的预测价值。      

微小RNA在食管癌诊断预后及治疗中的作用

食管癌是常见的恶性肿瘤之一.在中国,其发病率和死亡率仅次于肺癌、胃癌和肝癌,居第4位[1].因其早期症状不典型、生理解剖部位特殊和临床缺乏有效的早期诊断方法,多数食管癌患者确诊时已属晚期而无法施行根治性外科治疗,因此早期诊断对食管癌的防治具有十分重要的意义.微小RNA(miRNAs)已被证实与食管癌的发生、发展密切相关,系统全面地了解并应用miRNAs,对食管癌的早期诊断、预后判断和治疗均大有裨益.     

miR-485-5p在恶性肿瘤中的研究进展

MicroRNAs(miRNAs)是一类长度约22个核苷酸的非编码RNA,在基因表达调控中,参与多种重要的生理和病理过程。miRNAs能够特异性结合靶基因序列,抑制基因的转录或翻译,从而抑制基因在转录或转录后水平上的表达。miRNAs作为肿瘤抑制因子或促进因子在癌症发生发展中经常失调。最近的研究发现miR-485-5p在多种癌症中表达下调,并调控肿瘤细胞生长、增殖、侵袭和迁移。miR-485-5p在肿瘤诊断、治疗及预后相关方面可作为具有潜在价值的肿瘤标志物,并有望成为临床肿瘤靶向治疗的新的治疗靶点。本文围绕miR-485-5p在肝癌、胃癌、乳腺癌及其他恶性肿瘤中的研究进展展开综述并对其未来应用和发展进行展望。     

microRNAs与胃癌治疗

microRNAs（miRNAs）是真核生物中一类小分子非编码单链RNA,在转录后水平上调控靶mRNA的表达。目前,miRNA功能学研究发现miRNA与胃癌的侵袭转移、化疗耐药、放疗增敏、血管形成、基因甲基化、诊断和预后有直接关系,提示miRNA有可能成为肿瘤治疗的新思路。本文将阐述miRNA和胃癌放化疗的关系及其作为诊断、预后因子和基因治疗靶点基础研究方面的新进展。     

胃癌转移相关miRNA的差异表达谱及miR-218的生物学分析

目的 探讨胃癌转移相关微小RNA（miRNA）的差异表达情况并进行miR-218的生物学分析。方法 采用实时荧光定量PCR（qPCR）及miRNA芯片法检测低转移潜能的胃癌细胞亚系（SGC7901-NM、MKN28-NM）与高转移潜能的胃癌细胞亚系（SGC7901-M、MKN28-M）间miRNA的差异表达。提取不同转移潜能胃癌细胞系和10例胃癌冰冻组织及相应的转移淋巴结中的总RNA,利用qPCR检测miR-218在不同细胞及组织中的表达情况。结果 对不同转移潜能的胃癌细胞亚系进行芯片检测发现,与SGC7901-NM细胞比较,SGC7901-M 细胞有47个分子表达下调,15个分子表达上调。与MKN28-NM细胞比较,MKN28-M细胞有41个分子表达下调,83个分子表达上调。在SGC7901-M及MKN28-M细胞中,34个分子表达均出现下降,11个分子表达均出现上升。对不同转移潜能的胃癌细胞亚系以及人永生化正常胃黏膜细胞系GES进行检测可以发现,4种不同转移潜能的胃癌细胞亚系中miR-218的表达均低于正常胃黏膜细胞系GES,差异有统计学意义（P＜0.05）,且在高转移潜能胃癌细胞亚系中miR-218的表达均低于低转移潜能胃癌细胞系,差异有统计学意义（P＜0.05）。胃癌转移淋巴结中miR-218的表达水平为0.23±0.02,低于胃癌原发灶的1.09±0.05,差异有统计学意义（P＜0.05）。结论 胃癌转移相关miRNA会出现差异表达情况,高转移潜能胃癌细胞中的miR-218表达水平上调可能与胃癌转移存在一定关系。     

微小RNA与胃癌的研究进展

 微小RNA(microRNA,简称miRNA),是一类生物体内源性的非编码小RNA,在转录后水平上对基因的表达进行负调控,导致mRNA的降解或翻译抑制。影响细胞分化、增殖、凋亡、癌变等多个方面,在整个生物发育过程中产生重要的作用,miRNA可以作为癌基因或抑癌基因在胃癌中发挥作用,本文就miRNA在胃癌中的表达及其作用研究进展作一综述。     

Loss of has-miR-337-3p expression is associated with lymph node metastasis of human gastric cancer

Background

Metastasis is the major cause of cancer-related death in patients with gastric cancer, and aberrant expression of various microRNAs (miRNAs) is associated with cancer metastasis.

Methods

Profiling of differentially expressed miRNAs was performed in three cases of primary gastric cancer and the corresponding metastatic lymph node tissues. Then, the five most altered miRNAs were further verified in 16 paired samples. Two of these five miRNAs were further assessed for their effects on the regulation of gastric cancer cell growth and invasion.

Results

The miRNA profile data showed 151 upregulated miRNAs (≥ 1.5-fold) and 285 downregulated miRNAs (≤ 0.67-fold) in the metastatic tissues compared to the primary gastric cancer tissues. Among these five miRNAs (i.e., hsa-miR-508-5p, hsa-miR-30c, hsa-miR-337-3p, hsa-miR-483-5p, and hsa-miR-134), expression of hsa-miR-337-3p and hsa-miR-134 was significantly downregulated in these 16 lymph node metastatic tissues compared to their primary tumor tissues (P<0.05) and in nine gastric cancer cell lines compared to the nonmalignant GES cell line. Furthermore, induction of hsa-miR-134 or hsa-miR-337-3p expression did not dramatically affect gastric cancer cell proliferation, but transfection of the hsa-miR-337-3p mimic did reduce gastric cancer cell invasion capacity.

Conclusions

These findings indicate that hsa-miR-337-3p plays a role in the reduction of gastric cancer cell invasion capacity, and further studies on the mechanism of hsa-miR-337-3p in gastric cancer metastasis are warranted.     

The Functions of MicroRNAs and Their Potential Applications in the Diagnosis and Treatment of Gastric Cancer

Gastric cancer is a highly malignant disease with complex pathogenic mechanisms, and has high incidence and mortality rate. At present, the diagnosis of gastric cancer mainly includes gastroscopy, serum analysis and needle biopsy, and the treatment methods include conventional surgical resection, radiotherapy and chemotherapy. Yet, some limitations were involved in these diagnostic and therapeutic methods, so accurate targeted therapy has received considerable attention. MicroRNAs (miRNAs) are non-coding RNA that can interact with the 3-terminal non-translational region of the target gene mRNA to reduce the expression of the target gene, participate in the regulation of multiple signaling pathways, and play an important role in life activities of the cell. More and more studies have shown that miRNAs can participate in the formation and development of cancer, and many abnormally expressed miRNAs in gastric cancer cells are considered to be potential targets for clinical diagnosis and treatment of gastric cancer. This paper summarizes research progress of miRNAs in gastric cancer, and aims to provide new ideas for the diagnosis and treatment of gastric cancer.     

Identification of new aberrantly expressed miRNAs in intestinal-type gastric cancer and its clinical significance

miRNAs are small 19 to 22 nucleotide sequences of RNA that negatively regulate gene expression. miRNA expression profiles may become useful biomarkers for diagnostics, prognosis and prediction of response to treat, and it could be a powerful tool for cancer prevention and therapeutics. Several miRNA expression profiles of miRNAs in gastric cancer have been reported, but these studies screened only few miRNAs and samples used in experiments include several different subtypes of gastric cancers, which decrease the sensitivity to identify new aberrant miRNAs. In this study, a miRNA expression profile was identified by miRCURY LNA Array (v.14.0) between intestinal-type gastric cancers and normal tissues. Forty miRNA precursors were up-regulated and thirty-six miRNA were down-regulated in intestinal-type gastric cancers (p<0.01). Sixteen new miRNAs were found in intestinal-type gastric cancers. Seventeen new miRNAs were found in intestinal-type gastric cancers. miR-145, miR-27a, miR-494 are differently expressed between intestinal-type and diffuse-type gastric cancers. miR-32, miR-182 and miR-143 dysregulated expression levels are related with different pathological stages of intestinal-type gastric cancers (p<0.01). Taken together, aberrantly expressed miRNAs may offer new clues to tumorigenesis of gastric cancers. miR-32, miR-182 and miR-143 may be potential diagnostic biomarkers for intestinal-type gastric cancers.     

MicroRNA profiling of gastric cancer patients from formalin-fixed paraffin-embedded samples

MicroRNA (miRNA) is a small non-coding RNA that targets specific mRNA. Recent progress in the extraction of RNA from formalin-fixed paraffin-embedded (FFPE) tissues has facilitated miRNA profiling using samples stored in laboratories worldwide. In the present study, miRNA profiling of gastric cancer patients is determined using FFPE samples. First, criteria were established for determining evaluable RNA from the FFPE samples. miRNA profiling was then undertaken using miRNA oligo chips with 885 featured genes. The FFPE samples were obtained from 47 gastric cancer patients who underwent operations between 1997 and 2007. Results showed that out of 47 paired samples, 37 pairs (78.8%) were evaluable by our criteria. A total of 30 miRNAs were significantly up-regulated and 11 miRNAs were down-regulated in gastric cancer compared with those in normal gastric tissue. Among these, 14 miRNAs, including miR-21, were identified as prognostic factors of gastric cancer patients. Furthermore, miR-34a was selected as an independent prognostic factor. In conclusion, we identified miRNAs that are associated with the prognosis of gastric cancer patients. miRNA profiling using FFPE samples is a useful and promising method of evaluation for samples stored in laboratories worldwide, and can generate extremely valuable clinical data.