miR-363-3p Inhibits Osteosarcoma Cell Proliferation and Invasion via Targeting SOX4

miR-363-3p has been shown to suppress tumor growth and metastasis in various human cancers. However, the function of miR-363-3p in osteosarcoma (OS) has not been determined. In our study, we found that the expression of miR-363-3p was significantly downregulated in OS tissues compared with adjacent normal tissues. miR-363-3p expression was associated with the poor overall survival rate of OS patients. Moreover, we found that overexpression of miR-363-3p markedly inhibited the proliferation, migration, and invasion of U2OS and MG63 cells. Moreover, we found that SOX4 was a direct target of miR-363-3p in OS cells. Overexpression of miR-363-3p significantly inhibited the expression of SOX4. Expression levels of miR-363-3p and SOX4 were negatively correlated in OS tissues. Finally, we found that restoration of SOX4 attenuated the suppressive effects of miR-363-3p on the proliferation, migration, and invasion of U2OS and MG63 cells. Therefore, our findings demonstrated that miR-363-3p served as a tumor suppressor in OS tissues by targeting SOX4.     

Circulating miR-21-5p and miR-148a-3p as emerging non-invasive biomarkers in thymic epithelial tumors

Thymic epithelial cells give rise to both thymoma and thymic carcinoma. A crucial advance in thymic epithelial tumors (TET) management may derive from the identification of novel molecular biomarkers able to improve diagnosis, prognosis and treatment planning.In a previous study, we identified microRNAs that were differentially expressed in tumor vs normal thymic tissues. Among the microRNAs resulted up-regulated in TET tissues, we evaluated miR-21-5p, miR-148a-3p, miR-141-3p, miR-34b-5p, miR-34c-5p, miR-455-5p as blood plasma circulating non-invasive biomarkers for TET management.We firstly report that the expression levels of specific onco-miRNAs, that we found upregulated in the blood plasma collected from TET patients at surgery, resulted significantly reduced in follow-up samples.This pilot study suggests that circulating miR-21-5p and miR-148a-3p could represent novel non-invasive biomarkers to evaluate the efficacy of therapy and the prognosis of TET.     

miR-124 and miR-506 inhibit colorectal cancer progression by targeting DNMT3B and DNMT1

miR-124 and miR-506 are reportedly down-regulated and associated with tumor progression in many cancers, but little is known about their intrinsic regulatory mechanisms in colorectal cancer (CRC). In this study, we found that the miR-124 and miR-506 levels were significantly lower in human CRC tissues than in controls, as indicated by qRT-PCR and in situ hybridization histochemistry. We also found that the overexpression of miR-124 or miR-506 inhibited tumor cell progression and increased sensitivity to chemotherapy in vitro. Increased miR-124 or miR-506 expression also inhibited tumor cell proliferation and invasion in vivo. Luciferase reporter assays and western blotting were used to determine the association between miR-124, miR-506 and their target genes, DNMTs. We further identified that miR-124 and miR-506 directly targeted DNMT3B and indirectly targeted DNMT1. The overexpression of miR-124 and miR-506 reduced global DNA methylation and restored the expression of E-cadherin, MGMT and P16. In conclusion, our data showed that miR-124 and miR-506 inhibit progression and increase sensitivity to chemotherapy by targeting DNMT3B and DNMT1 in CRC. These findings may provide novel avenues for the development of targeted therapies.     

MiR-128-3p靶向抑制HOXA5调控多形性胶质母细胞瘤的增殖、侵袭与凋亡

目的 探索HOXA5在胶质母细胞瘤（GBM）中高表达的原因及miR-128-3p调控胶质母细胞瘤进展的分子机制。方法 通过慢病毒转染上调或下调U87细胞中miR-128-3p的表达水平,再利用蛋白质免疫印迹法检测HOXA5的表达水平的变化来探索miR-128-3p与HOXA5在GBM中表达的相关性。利用双荧光素报告基因实验验证miR-128-3p对HOXA5的靶向抑制关系。利用miR-128-3p与HOXA5过表达的质粒转染U87细胞进行拯救实验,通过CCK-8、Transwell、流式细胞学分析与裸鼠体内实验验证miR-128-3p调控GBM增殖、侵袭及凋亡方面的分子机制。结果 上调U87细胞中miR-128-3p表达后HOXA5的表达水平显著下降,下调U87细胞中miR-128-3p表达后HOXA5表达水平明显升高（P<0.05）,两者表达呈显著负相关。miR-128-3p可靶向结合HOXA5基因的3’UTR区并抑制HOXA5表达。miR-128-3p+Control组U87细胞增殖、侵袭及抗凋亡能力显著下降。结论 miR-128-3p可通过靶向抑制HOXA5负向调控GBM细胞的增殖、侵袭及抗凋亡能力,HOXA5在GBM中呈高表达与miR-128-3p表达水平降低有关。     

lncRNA MNX1-AS1 Promotes Glioblastoma Progression Through Inhibition of miR-4443

Long noncoding RNAs (lncRNAs) have been acknowledged as important regulators in various human cancers. lncRNA MNX1-AS1 has been shown to be an oncogene in epithelial ovarian cancer. However, the function of MNX1-AS1 in glioblastoma (GBM) remains largely unknown. Here we found that the expression of MNX1-AS1 was significantly upregulated in GBM tissues and cell lines. Knockdown of MNX1-AS1 significantly inhibited the proliferation, migration, and invasion of GBM cells. In terms of mechanism, we found that MNX1-AS1 could bind to miR-4443 in GBM cells. Overexpression of miR-4443 significantly inhibited the expression of MNX1-AS1 and vice versa. Moreover, there was an inverse correlation between the expression levels of MNX1-AS1 and miR-4443 in GBM tissues. We found that overexpression of miR-4443 inhibited the proliferation, migration, and invasion of GBM cells. We also showed that inhibition of miR-4443 reversed the effects of MNX1-AS1 knockdown on GBM cell proliferation, migration, and invasion. Taken together, we found that MNX1-AS1 promoted the proliferation, migration, and invasion of GBM cells through inhibiting miR-4443.     

DNMT1和p27蛋白在原发性与继发性胶质母细胞瘤中的表达及相关性

目的 探讨原发性胶质母细胞瘤和继发性胶质母细胞瘤中DNA甲基转移酶1（DNMT1）蛋白及p27蛋白的表达及相关性。方法 收集2000年1月1日至2012年12月31日经手术切除胶质母细胞瘤患者组织蜡块标本64例（原发胶质母细胞瘤32例,继发性胶质母细胞瘤32例）作为研究对象。检测64例胶质母细胞瘤标本和13例正常脑组织中DNMT1蛋白及p27蛋白的表达情况。结果 在正常脑组织中,DNMT1蛋白不表达,而在原发性和继发性胶质母细胞瘤中的阳性表达率分别为59.4%和81.3%。在正常脑组织中,p27蛋白的阳性表达率为100.0%,高于其在原发性和继发性胶质母细胞瘤中的50.0%和25.0%（P<0.05）。DNMT1 蛋白及p27蛋白在原发性和继发性胶质母细胞瘤中的表达差异存在统计学意义 （P<0.05）,但两者表达无相关性（r=0.41,P>0.05）。结论 DNMT1蛋白及p27蛋白在原发性和继发性胶质母细胞瘤中的表达存在差异,联合检测肿瘤标本中两者的表达情况有助于判断不同类型胶质母细胞瘤。     

鼻咽癌患者血清中miR-141-3p和miR-155-3p的表达水平及其临床意义

目的:探讨鼻咽癌患者血清中miR-141-3p及miR-155-3p的表达水平及临床意义.方法:选取2017年01月至2020年09月我院收治的95例鼻咽癌患者和45例健康对照组作为研究对象,采用实时荧光定量PCR法检测miR-141-3p及miR-155-3p表达水平.应用受试者工作特征(receiver opera...     

miR-497-5p靶向调控CCNE1基因抑制胰腺癌细胞增殖

目的明确miR-497-5p在胰腺癌(PaCa)中的表达及临床意义,并探究其对PaCa细胞增殖的影响及机制。方法实时荧光定量PCR实验检测miR-497-5p的表达,卡方检验和Kaplan-Meier生存法分析miR-497-5p的表达与临床病理特征及预后的关系;CCK-8实验和流式细胞术检测过表达miR-497-5p对Capan-2和PANC-1细胞增殖和周期的影响,Spearman相关性检验分析miR-497-5p表达与G₁/S特异性细胞周期蛋白E1(cyclin E1,CCNE1)mRNA表达的关系;双荧光素酶报告基因实验和蛋白质印迹法验证miR-497-5p对CCNE1表达的调控作用。结果 miR-497-5p在癌组织中的表达显著低于癌旁正常组织(P<0.001),T3+T4期患者癌组织中miR-497-5p的表达显著低于T1+T2期癌组织(P<0.001);低表达miR-497-5p与较高的T分期相关(P=0.003);低表达miR-497-5p的患者5年总体生存率显著低于高表达者(P=0.036)。与对照组相比,miR-497-5p过表达组...     

LncRNA SNHG5靶向miR-421调控胶质母细胞瘤细胞增殖、侵袭和凋亡的机制CSCD

目的探讨SNHG5靶向miR-421调控多形性胶质母细胞瘤(GBM)发生与发展的分子机制。方法收集31例GBM肿瘤与32例正常脑组织标本,实时荧光定量PCR法检测标本中SNHG5与miR-421的表达水平;通过慢病毒或质粒转染U87细胞上调或下调SNHG5的表达水平,采用实时荧光定量PCR检测转染后U87细胞中miR-421的表达水平,分析GBM中miR-421与SNHG5表达的相关性。双荧光素报告基因实验验证SNHG5对miR-421的靶向关系。利用SNHG5与miR-421两者均低表达的质粒转染U87细胞进行拯救实验,通过CCK-8、Transwell、流式细胞学分析及裸鼠体内实验验证SNHG5通过靶向miR-421调控GBM细胞增殖、侵袭及凋亡。结果上调U87细胞中SNHG5表达后miR-421的表达水平显著下降,下调U87细胞中SNHG5表达后miR-421表达水平明显升高(P<0.05),两者表达呈显著负相关。双荧光素酶报告基因实验结果提示SNHG5可靶向结合miR-421。拯救实验结果表明,相比si-SNHG5+miR-421-inhibitor组,si-SNHG5+control-inhibitor组的U87细胞增殖、侵袭及抗凋亡能力均显著下降,且BAX与p21蛋白表达水平升高,CyclinD1与Bcl-2蛋白表达显著下降(P<0.05)。结论SNHG5可通过靶向miR-421并影响CyclinD1、p21、BAX、Bcl-2蛋白表达进而促进GBM细胞的增殖、侵袭及抗凋亡行为。miR-421在GBM中呈低表达与SNHG5表达水平升高有关。     

MicroRNA-338-3p Inhibits Proliferation and Promotes Apoptosis of Multiple Myeloma Cells Through Targeting Cyclin-Dependent Kinase 4

MicroRNA-338-3p (miR-338-3p) has been reported to be a tumor suppressor in multiple cancer types. However, the biological role of miR-338-3p and its underlying mechanism in multiple myeloma (MM) remain unclear. In the present study, we investigated the biological role and potential of miR-338-3p in MM. We found that miR-338-3p was significantly decreased in newly diagnosed and relapsed MM tissues and cell lines. Overexpression of miR-338-3p in MM cells significantly inhibited proliferation and promoted apoptosis, caspase 3, and caspase 8 activity. Bioinformatics algorithm analysis predicted that cyclin-dependent kinase 4 (CDK4) was a direct target of miR-338-3p, and this was experimentally verified by a dual-luciferase reporter assay. Furthermore, overexpression of miR-338-3p inhibited CDK4 expression on mRNA and protein levels. Of note, the restoration of CDK4 expression markedly abolished the effect of miR-338-3p overexpression on cell proliferation, apoptosis, caspase 3, and caspase 8 activities in MM cells. Taken together, the present study is the first to demonstrate that miR-338-3p functions as a tumor suppressor in MM through inhibiting CDK4. This finding implies that miR-338-3p is a potential therapeutic target for the treatment of MM.     

人支气管上皮hsa-miR-148a-3p 低表达细胞株的建立

目的： 建立稳定的hsa-miR-148a-3p低表达人支气管上皮细胞株(16HBE)。方法：根据miRBase中提供的序列信息设计hsa-miR-148a-3p tough decoy RNA(TuD RNA),并将其连接到慢病毒载体pLKO.1-puro上。将重组慢病毒载体转染至293FT细胞并包装为慢病毒后,收集病毒上清,感染正常16HBE细胞。用嘌呤霉素筛选出has-miR-148a-3p低表达的16HBE细胞株,通过荧光定量PCR对其进行鉴定,然后对筛选出的细胞分别采用荧光定量PCR和Western blot检测DNA甲基转移酶1(DNMT1) mRNA和蛋白的表达水平。结果：测序结果表明含hsa-miR-148a-3p TuD RNA的重组慢病毒载体构建成功;荧光定量PCR检测显示has-miR-148a-3p低表达的16HBE细胞株has-miR-148a-3p的表达量比正常16HBE细胞低44%(P<0.01),其作用靶基因DNMT1的mRNA和蛋白表达水平分别为正常细胞的3.4倍和2.0倍(P均<0.01)。结论：成功建立hsa-miR-148a-3p低表达的16HBE细胞,hsa-miR-148a-3p的低表达能提高DNMT1 mRNA和蛋白的表达水平。     

Upregulation of miR-324-5p Inhibits Proliferation and Invasion of Colorectal Cancer Cells by Targeting ELAVL1

Colorectal cancer (CRC) is a common clinical cancer that remains incurable in most cases. miRNAs are reported to play a part in the development of various tumors. In the present study, we found that miR-324-5p was downregulated in CRC cells, while ELAV (embryonic lethal, abnormal vision, Drosophila)-like protein 1 (ELAVL1) showed a higher expression. miR-324-5p transfection significantly inhibited the proliferation as well as invasion in both SW620 and SW480 cells. miR-324-5p mimic transfection markedly decreased the expression of ELAVL1. Luciferase reporter gene assay confirmed that ELAVL1 is a direct target of miR- 324-5p. Furthermore, cancer invasion factors uPA, uPAR, and MMP-9 were found to drop significantly in miR-324-5p-transfected groups. To conclude, our findings indicate that miR-324-5p may play a suppressive role in colorectal cell viability and invasion, at least in part, through directly targeting ELAVL1. Therefore, miR-234-5p might function as a promising candidate for CRC treatment and deserves deeper research.     

miR-363-3p和miR-5100在非小细胞肺癌中的表达及其临床意义

目的:探讨小分子RNA(microRNA)miR-363-3p 和miR-5100在非小细胞肺癌中的表达及其临床意义.方法:利用荧光定量PCR的方法,检测肿瘤组织、癌旁组织及远离肿瘤的正常组织中致癌基因Myc的mRNA 和miR-363-3p、miR-5100的表达,然后分析miR-363-3p 和miR-5100与临床病理特征之间的相关性.结果:Myc在肿瘤组织中表达明显升高;miR-363-3p在肺癌组织中的表达明显低于正常组织(P<0.001),而在癌旁组织中的表达却远远高于正常组织(P<0.05);miR-5100在肺癌组织中的表达显著地高于正常组织(P<0.001),并且癌旁组织中的表达也高于正常组织(P<0.05).临床相关性分析显示,miR-363-3p的表达与淋巴结转移呈正相关(P<0.001),miR-5100的表达与临床分期也呈正相关性(P<0.05).结论:miR-363-3p 和miR-5100可能参与了非小细胞肺癌早期的发生和转移,并可能作为早期诊断和预后的分子标志物.     

The Effects of Combination of Mimic miR-155-5p and Antagonist miR-324-5p Encapsulated Chitosan in Ovarian Cancer SKOV3

Objective: Ovarian cancer is a malignant tumor that attacks reproductive organs of women. MicroRNA is known to have an involvement in the prognosis of ovarian cancer. One of them is miR-155-5p which is down regulated and miR-324-5p which is up regulated. Chitosan is used as microRNA delivery system. The aims of this study is to find out the effects of combination microRNA encapsulated chitosan in cell line SKOV3. Methods: Cell line SKOV3 obtained from Stem Cell and Cancer Institute (Kalbe). Mimic miR-155-5p and Antagonist miR-324-5p formulated with chitosan. Total RNA was extracted from nine samples (three as control and six as treatment), and prepared for cDNA synthesis. Expression of RNA and mRNA target was measured using q-PCR Biorad CFX96 C.100 and Gen Ex 7 software. Statistics analysis was measured using SPSS 16.0. Results: The administration of combination microRNA encapsulated with chitosan affect the expression of miR-155-5p and miR-324-5p endogen (p <0.05). The expression of mRNA target HIF1α and GLI1 was down regulated after treatment. The correlation between expression of microRNA and mRNA target was strongly (p <0.05). Conclusion: This study successfully presented effects of combination of mimic miR-155-5p and antagonist miR-324-5p encapsulated chitosan which be considered as a potential therapy targets for ovarium cancer.     

miR-454-3p在恶性肿瘤中的研究进展

近年来,越来越多的国内外研究显示微小RNA（microRNA,miRNA）与恶性肿瘤的发生、发展过程紧密相连。因此,miRNA成为目前肿瘤研究的新热点。miR-454-3p不仅在许多恶性肿瘤中异常表达,同时也发挥着重要作用。本文就miR-454-3p在各种恶性肿瘤中的表达、作用以及调控机制作一综述。     

结肠癌细胞中miR-145-5p、miR-143-3p的表达变化对多药耐药的影响

目的:探讨人结肠癌细胞中miR-145-5p、miR-143-3p的表达发生变化后对P-gp和MRP的影响。方法:采用Western Blot和qRT-PCR法检测人结肠癌细胞分别转染miR-145-5p mimics/inhibitor、miR-143-3p mimics/inhibitor后P-gp 和MRP的表达。结果:转染miR-145-5p mimics后P-gp和MRP的蛋白和基因表达均降低（P<0.05）,转染miR-145-5p inhibitor后P-gp 和MRP的蛋白和基因表达均升高（P<0.05）。转染miR-145-5p mimics NC和miR-145-5p inhibitor NC后P-gp 和MRP的蛋白和基因表达无明显变化（P>0.05）。转染miR-143-3p mimics后P-gp和MRP的蛋白和基因表达均降低（P<0.05）,miR-143-3p inhibitor后P-gp和MRP的蛋白和基因表达均升高（P<0.05）。转染miR-143-3p mimics NC和miR-143-3p inhibitor NC后P-gp 和MRP的蛋白和基因表达无明显变化（P>0.05）。结论:miR-145-5p及miR-143-3p对多药耐药蛋白P-gp、MRP具有调控作用,参与了结肠癌的多药耐药。     

miR-331-3p在恶性肿瘤中的研究进展

miRNA是一种存在于真核生物细胞中的一类内源性非编码的RNA小分子,miR-331-3p作为miRNA家族中的一员,在细胞生理过程中发挥重要作用。近年来,miR-331-3p在恶性肿瘤中的作用日益受到关注。已有研究显示,miR-331-3p在宫颈癌、肝癌、胶质母细胞瘤及前列腺癌等恶性肿瘤的发生发展及复发转移过程中均发挥着重要作用。这些研究结果对恶性肿瘤的诊断及预后起到帮助作用。     

miR-325-3p靶向CLDN1基因调控胃癌上皮间质转化和侵袭转移

目的 探讨miR-325-3p靶向CLDN1基因对胃癌上皮间质转化和侵袭转移的影响.方法 选取人胃黏膜上皮细胞株GES-1以及人胃癌细胞株HGC27、SGC-7901、MKN-45和MGC-803,并检测细胞中miR-325-3p和CLDN1的表达.双荧光素酶报告实验验证miR-325-3p和CLDN1的靶向关系,干预...