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.     

miR-615 Inhibits Prostate Cancer Cell Proliferation and Invasion by Directly Targeting Cyclin D2

Previous studies have reported that miR-615 exerts a tumor suppressor role in some tumors, such as esophageal squamous cell carcinoma and non-small cell lung cancer. However, the role of miR-615 in prostate cancer has not been defined. Here we found that miR-615 was downregulated in prostate cancer tissues and cell lines. Overexpression of miR-615 in PC-3 cells significantly inhibited cellular proliferation, migration, and invasion. Moreover, overexpression of miR-615 delayed tumor growth in vivo. In terms of mechanism, we found that cyclin D2 (CCND2) is a target gene of miR-615 in prostate cancer. We showed that miR-615 could bind to the 3 -UTR region of CCND2 mRNA and inhibit its expression. There was a negative correlation between the expression of miR-615 and CCND2 in prostate cancer tissues. Moreover, restoration of cyclin D2 abolished the inhibitory effects of miR-615 on the proliferation, migration, and invasion of prostate cancer cells. Taken together, our study identified miR-615 as a tumor suppressor by targeting cyclin D2 in prostate cancer.     

Mir-1247 Affects the Proliferation,Invasion and Apoptosis of Osteosarcoma Cells through SOX9

Objective: This study aimed to explore the miR-1247-mediated promotion of osteosarcoma (OS) cell proliferation by SOX9. Methods: We recruited 97 OS patients admitted to our hospital (the observation group, OG) and 82 healthy people undergoing physical examinations (the control group, CG) over the same period into this study. The expression of miR-1247 and SOX9 in human OS cells in vitro was tested to determine the effect of miR-1247 and SOX9 on OS and to analyze the relationship between miR-1247 and SOX9. Results: We detected lowly expressed miR-1247 and highly expressed SOX9 in the peripheral blood of OS patients (P < 0.05). Both miR-1247 and SOX9 showed good performances in diagnosing OS. OS cells (143B cells) in the miR-1247-mimics group showed markedly lower cell proliferation and invasion rates and higher apoptosis rates than cells in the miR-1247-inhibitor group and the miR-NC group (P < 0.05). 143B cells in the sh-SOX9 group showed higher proliferation and invasion rates and lower apoptosis rates than cells in the si-SOX9 group and the NC group (P < 0.05). SOX9 protein concentrations were lower in cells in the miR-1247-mimics group than in cells in the miR-1247-inhibitor group and the miR-NC group (P < 0.05), with higher SOX9 protein concentrations in the miR-1247-inhibitor group than in the miR-NC group (P < 0.05). Conclusion: MiR-1247 is lowly expressed in OS. It can promote the proliferation and invasion of OS cells and accelerate the progression of OS by mediating SOX9.     

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。     

miR-223负调控SOX9对胶质瘤生物学行为的影响

目的:探讨miRNA通过靶向调控促癌基因SOX9的表达影响胶质瘤生物学行为的作用及机制。方法:采用qRT-PCR检测miR-223在WHO分级低级别(Ⅰ和Ⅱ)与高级别(Ⅲ和Ⅳ)脑胶质瘤组织和癌旁正常组织中的表达水平,miR-223在正常人星形胶质细胞、A172、U251、U87和U373胶质瘤细胞中的表达水平。采用生物信息软件预测SOX9是miR-223的潜在靶基因,并通过双荧光素酶报告基因实验进行验证。采用qRT-PCR、Western blot检测SOX9在各WHO分级脑胶质瘤组织和各脑胶质瘤细胞株中的表达。多种体外实验检测miR-223和SOX9对脑胶质瘤细胞增殖,侵袭、迁移及周期的影响。构建脑胶质瘤裸鼠移植瘤模型,检测miR-223对体内移植瘤生长的影响。结果:miR-223在脑胶质瘤组织及脑胶质瘤细胞中均呈现低表达,并且通过抑制靶基因SOX9的靶向调控作用抑制脑胶质瘤细胞恶性生物学行为。同时脑胶质瘤裸鼠移植瘤模型中,miR-223过表达可下调SOX9的表达水平并抑制裸鼠体内移植瘤的生长。结论:miR-223通过抑制靶基因SOX9的表达水平在胶质瘤中扮演抑癌基因的角色,提示其具有成为胶质瘤诊疗新靶点的潜力。     

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.     

miR-601靶向调控MMP-17抑制非小细胞肺癌的迁移和侵袭CSCD

目的探讨miR-601对非小细胞肺癌(NSCLC)迁移和侵袭能力的影响并探讨其可能的作用机制。方法RT-qPCR检测NSCLC组织中miR-601的表达,并分析表达水平与癌细胞侵袭和淋巴结转移的相关性。将miR-601 mimics瞬时转染A549细胞或H1299细胞,Transwell实验检测其对两种细胞迁移和侵袭能力的影响。生物信息学预测miR-601相关靶基因,采用双荧光素酶实验进行靶基因验证。检测miR-601的靶基因对A549细胞或H1299细胞迁移及侵袭能力的影响。结果miR-601在NSCLC组织中表达明显降低(P<0.001),且降低水平与癌细胞的浸润(P<0.007)及淋巴结转移(P<0.011)密切相关。瞬时转染miR-601 mimics能明显抑制A549细胞或H1299细胞的迁移及侵袭能力。生物信息学及荧光素酶报告实验提示MMP-17是miR-601的靶基因。MMP-17能促进A549细胞或H1299细胞的迁移和侵袭,但其促进迁移侵袭的能力可被miR-601抑制。结论miR-601通过靶向调控MMP-17而抑制非小细胞肺癌的迁移和侵袭。     

MiR-129-5p靶向HMGB1抑制骨肉瘤细胞增殖和迁移

目的 探讨miR-129-5p对骨肉瘤(OS)细胞增殖和迁移的影响以及对HMGB1的调控作用.方法 RT-PCR和Western blot法分别检测骨肉瘤细胞株MG-63、Saos-2和成骨细胞hFOB1.19中miR-129-5p和HMGB1的表达.生物信息学预测miR-129-5p与HMGB1基因是否存在结合位点,...     

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 HOXA11-AS Promotes Proliferation and Migration via Sponging miR-155 in Hypopharyngeal Squamous Cell Carcinoma

Hypopharyngeal squamous cell carcinoma (HSCC) remains one of the most lethal malignancies in the head and neck. Long noncoding RNA (lncRNA) HOXA11-AS is proven to function as an oncogene and a therapeutic target in various tumors. Our previous study and others have demonstrated that HOXA11-AS is one of the most upregulated lncRNAs in HSCC. However, the role of HOXA11-AS in HSCC has not yet been identified. The current study demonstrated that the expression of HOXA11-AS was significantly upregulated in HSCC tumors and was positively associated with lymph node metastasis. Moreover, functional experiments revealed that HOXA11-AS knockdown suppressed the proliferation and migration potential in FaDu cells. Furthermore, luciferase reporter gene assay combined with cellular functional experiments demonstrated that HOXA11-AS functioned as a molecular sponge for miR-155, and inhibition of miR-155 attenuated the suppressive effect of HOXA11-AS knockdown on the aggressive phenotype in HSCC. This study identifies a tumor-promoting role of HOXA11-AS in HSCC and suggests HOXA11-AS might be a potential diagnostic and therapeutic target for HSCC.     

miR-374 a对肺腺癌细胞增殖与侵袭迁移的影响

目的 探究分析miR-374a对非小细胞肺癌细胞增殖、侵袭、迁移等生物学行为能力的影响.方法 采用RT-PCR检测miR-374a在正常肺上皮细胞CCD-8L及非小细胞肺癌细胞A549、H1975中的表达情况.采用miR-374a mimic和miR-374a inhibitor转染非小细胞肺癌细胞A549、H1975...     

miR-192在胶质瘤U251细胞中的表达及对其增殖、迁移及凋亡能力的影响

目的 探讨miR-192在胶质瘤U251细胞中的表达及对其增殖、迁移及凋亡等生物学能力的影响.方法 采用RT-PCR检测胶质瘤细胞株U251、LN18、U373和正常人脑胶质细胞株中HEB的表达水平.采用脂质体转染法将miR-192类似物(miR-192 mimics)和阴性对照(miR-negtive control...     

miR-30c在骨肉瘤组织中的表达及其临床意义

目的:探讨miR-30c在骨肉瘤组织中的表达及其临床意义。方法:37例骨肉瘤组织标本均来自于2007年1月至2015年1月间在新疆医科大学第六附属医院住院接受治疗的骨肉瘤患者,实时定量PCR和原位杂交分析骨肉瘤组织中miR-30c表达情况。单因素和多因素分析miR-30c表达与骨肉瘤临床病理参数和预后之间的相关性。结果:实时定量PCR检测和原位杂交检测分析结果一致表明:骨肉瘤组织中miR-30c的表达水平显著低于正常骨组织,差异有统计学意义（P＜0.05）;miR-30c低表达组肿瘤与更晚分期和中低分化程度、肿瘤复发有相关性（P＜0.05）;多元回归分析表明,miR-30c低表达与骨肉瘤患者生存期更短有关(P＜0.01);miR-30c低水平表达是骨肉瘤患者预后的一个独立危险因数。结论:miR-30c表达下调能够促进肿瘤进展,是预测骨肉瘤患者预后的可靠指标,miR-30c也具有成为骨肉瘤靶向治疗靶点的潜力。     

miR-145通过靶向AP4对非小细胞肺癌A549细胞迁移侵袭的影响

 目的 探讨miR-145对非小细胞肺癌迁移与侵袭能力的影响及其可能的作用机制。方法 qRTPCR法检测非小细胞肺癌组织中miR-145和激活增强子结合蛋白4（activating enhancer binding protein4, AP4）mRNA的表达。A549细胞转染miR-145 mimic或者AP4 siRNA后，划痕实验与Transwell小室法分别检测A549细胞的迁移与侵袭能力，qRT-PCR法与免疫印迹法（Western blot）检测A549细胞中AP4 mRNA与蛋白表达水平；双荧光素酶报告基因法检测AP4 mRNA与miR-145的关系。结果 与癌旁正常组织相比，非小细胞肺癌组织中miR-145表达明显降低（P<0.05），而AP4 mRNA和蛋白表达均明显升高（均P<0.05）；与对照组相比，转染miR-145 mimic后，A549细胞中miR-145表达明显升高（P<0.05），AP4 mRNA和蛋白水平明显降低（P<0.05）；A549细胞的迁移数与侵袭能力均显著下降（均P<0.05）；双荧光素酶报告基因法验证AP4 mRNA是miR-145的靶基因。A549细胞转染AP4siRNA后，A549细胞的迁移数与侵袭数显著下降（均P<0.05）。结论 上调miR-145能抑制A549细胞的迁移与侵袭能力，可能与其抑制靶基因AP4表达有关。     

miR-30c negatively regulates the migration and invasion by targeting the immediate early response protein 2 in SMMC-7721 and HepG2 cells

miR-30c has been reported to act as a tumor suppressor and negatively regulate cancer metastasis by directly targeting metastasis associated genes; however, miR-30c has also been shown to promote the invasion of metastatic breast cancer cells, suggesting that miR-30c might be involved in cancer cell metastasis in different ways via targeting different genes. In this study, we demonstrated that over-expression and knockdown of immediate early response protein 2 (IER2) modulated the general capacity of the migration and invasion in hepatocellular carcinoma cell line SMMC-7721 and HepG2, whereas overexpression and knockdown of miR-30c decreased and promoted cell motility, respectively. Further studies revealed that miR-30c overexpression down-regulated the expression of IER2 protein but not its mRNA level, and miR-30c can directly target the 3’ untranslated region (3’UTR) of IER2, and subsequently reducing its expression. Moreover, we also showed that suppression of cell motility by miR-30c was partially rescued by IER2 re-expression. Our results indicated that miR-30c may function as a negative regulator in cell motility, with IER2 as a direct and functional target in SMMC-7721 and HepG2 cells.     

miR-9500靶向SMAD2调控肺腺癌细胞的迁移和侵袭

目的 探讨miR-9500通过靶向SMAD2调控肺腺癌细胞迁移侵袭的相关分子机制。方法 通过生物信息学分析筛选出miR-9500的核心靶基因,并对其进行GO功能和KEGG信号通路富集及生存分析。预测miR-9500与其关键靶基因SMAD2之间的靶向结合位点,双荧光素酶报告实验验证miR-9500与SMAD2之间是否存在直接靶向关系,qRT-PCR和Western blot检测miR-9500对SMAD2 mRNA和蛋白表达水平的影响。划痕、Transwell实验及基质胶侵袭实验分析miR-9500对肺腺癌细胞迁移侵袭能力的影响。结果miR-9500核心靶基因主要富集于癌症通路、TGF-β信号通路和黏着斑信号通路等。排名前10的核心靶基因中,只有VAMP2、SMAD2及RXRA的表达水平与肺腺癌患者的总生存期显著相关。miR-9500可靶向结合SMAD2来下调SMAD2的表达水平。且过表达miR-9500可显著抑制肺腺癌细胞的迁移和侵袭能力,并显著降低迁移侵袭标志蛋白MMP2、MMP9的表达水平。结论 miR-9500可通过靶向SMAD2抑制肺腺癌细胞的迁移侵袭,其可能作为抑癌因子在肺腺...