LINC01133 promotes hepatocellular carcinoma progression by sponging miR-199a-5p and activating annexin A2.
LINC01133 promotes hepatocellular carcinoma progression by sponging miR-199a-5p and activating annexin A2.
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DOI：
10.1002/ctm2.409
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发表时间：
2021-05
影响因子：
10.6
通讯作者：
Zhou SL
中科院分区：
文献类型：
--
作者：
Yin D;Hu ZQ;Luo CB;Wang XY;Xin HY;Sun RQ;Wang PC;Li J;Fan J;Zhou ZJ;Zhou J;Zhou SL
长链非编码rna （lncRNAs）在功能上与癌症的发生和进展相关。尽管基因拷贝数变异（CNV）在肝细胞癌（HCC）中很常见，但lncrna中的CNV如何影响HCC的进展和复发尚不清楚。我们的目的是确定CNV相关的lncRNA参与HCC的进展和复发，并阐明其潜在的机制和预后价值。我们分析了来自49例HCC患者的匹配癌性和非癌性肝脏样本的全基因组测序（WGS）数据，以鉴定具有CNV的lncrna。结果通过TaqMan拷贝数测定在另一组238对HCC和非肿瘤样本中得到验证。我们进行了Kaplan - Meier分析和log - rank检验，以确定lncRNA CNV与预后的价值。我们进行了功能丧失和功能获得研究，以探索LINC01133在体外和体内的生物学功能。通过microRNA测序（miR‐seq）、实时定量PCR （qRT‐PCR）、western blot和双荧光素酶报告基因分析，阐明了竞争内源性rna （ceRNAs）的机制。我们通过RNA拉下、RNA免疫沉淀、qRT - PCR和western blot分析证实了lncRNA与蛋白的结合机制。LINC01133基因组拷贝数在HCC中增加，这与LINC01133的表达升高呈正相关。LINC01133拷贝数增加预示HCC患者预后不良。肝癌细胞中LINC01133过表达促进体外增殖和侵袭性表型，促进体内肿瘤生长和肺转移，而LINC01133敲低则相反。LINC01133海绵化miR‐199a‐5p，导致SNAI1表达增强，从而诱导HCC细胞上皮细胞向间充质细胞转化（EMT）。此外，LINC01133与Annexin A2 （ANXA2）相互作用，激活ANXA2/STAT3信号通路。LINC01133通过吸附miR - 199a - 5p和与ANXA2相互作用促进HCC进展。CNV增加可预测HCC患者预后不良。LINC01133基因组拷贝数在HCC中增加，与其表达升高呈正相关，LINC01133 CNV增加预示HCC患者预后不良。LINC01133海绵miR‐199a‐5p，导致SNAI1的表达增强，从而在HCC细胞中诱导EMT。LINC01133与ANXA2相互作用，激活ANXA2/STAT3信号通路。
Long noncoding RNAs (lncRNAs) are functionally associated with cancer development and progression. Although gene copy number variation (CNV) is common in hepatocellular carcinoma (HCC), it is not known how CNV in lncRNAs affects HCC progression and recurrence. We aimed to identify a CNV‐related lncRNA involved in HCC progression and recurrence and illustrate its underlying mechanisms and prognostic value. We analyzed the whole genome sequencing (WGS) data of matched cancerous and noncancerous liver samples from 49 patients with HCC to identify lncRNAs with CNV. The results were validated in another cohort of 238 paired HCC and nontumor samples by TaqMan copy number assay. We preformed Kaplan‐Meier analysis and log‐rank test to identify lncRNA CNV with prognostic value. We conducted loss‐ and gain‐of‐function studies to explore the biological functions of LINC01133 in vitro and in vivo. The competing endogenous RNAs (ceRNAs) mechanism was clarified by microRNA sequencing (miR‐seq), quantitative real‐time PCR (qRT‐PCR), western blot, and dual‐luciferase reporter assays. We confirmed the binding mechanism between lncRNA and protein by RNA pull‐down, RNA immunoprecipitation, qRT‐PCR, and western blot analyses. Genomic copy numbers of LINC01133 were increased in HCC, which were positively related with the elevated expression of LINC01133. Increased copy number of LINC01133 predicted the poor prognosis in HCC patients. LINC01133 overexpression in HCC cells promoted proliferation and aggressive phenotypes in vitro, and facilitated tumor growth and lung metastasis in vivo, whereas LINC01133 knockdown had the opposite effects. LINC01133 sponged miR‐199a‐5p, resulting in enhanced expression of SNAI1, which induced epithelial‐to‐mesenchymal transition (EMT) in HCC cells. In addition, LINC01133 interacted with Annexin A2 (ANXA2) to activate the ANXA2/STAT3 signaling pathway. LINC01133 promotes HCC progression by sponging miR‐199a‐5p and interacting with ANXA2. LINC01133 CNV gain is predictive of poor prognosis in patients with HCC. Genomic copy numbers of LINC01133 were increased in HCC, which were positively related with its elevated expression, and LINC01133 CNV gain predicted the poor prognosis in HCC patients. LINC01133 sponged miR‐199a‐5p, resulting in enhanced expression of SNAI1, which induced EMT in HCC cells. LINC01133 interacted with ANXA2 to activate ANXA2/STAT3 signaling pathway.
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影响因子：
13.5
作者：
Hu, Zhi-Qiang;Zhou, Shao-Lai;Zhou, Jian
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影响因子：
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作者：
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DOI：
10.1002/cac2.12108
发表时间：
2021-03
期刊：
Cancer communications (London, England)
影响因子：
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作者：
Tan YT;Lin JF;Li T;Li JJ;Xu RH;Ju HQ
通讯作者：
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影响因子：
30.8
作者：
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通讯作者：
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