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本文引用的文献

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METTL3-mediated mA modification of HDGF mRNA promotes gastric cancer progression and has prognostic significance.METTL3 介导的 HDGF mRNA mA 修饰促进胃癌进展并具有预后意义。
Gut. 2020 Jul;69(7):1193-1205. doi: 10.1136/gutjnl-2019-319639. Epub 2019 Oct 3.
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N-Methyladenosine Modulates Nonsense-Mediated mRNA Decay in Human Glioblastoma.N6-甲基腺苷调控人胶质母细胞瘤中无义介导的 mRNA 降解。
Cancer Res. 2019 Nov 15;79(22):5785-5798. doi: 10.1158/0008-5472.CAN-18-2868. Epub 2019 Sep 17.
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Expression patterns and prognostic value of mA-related genes in colorectal cancer.结直肠癌中与mA相关基因的表达模式及预后价值
Am J Transl Res. 2019 Jul 15;11(7):3972-3991. eCollection 2019.
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KIAA1429 acts as an oncogenic factor in breast cancer by regulating CDK1 in an N6-methyladenosine-independent manner.KIAA1429 通过非 N6-甲基腺苷依赖方式调控 CDK1 发挥致癌因子作用在乳腺癌中。
Oncogene. 2019 Aug;38(33):6123-6141. doi: 10.1038/s41388-019-0861-z. Epub 2019 Jul 8.
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CBX2 is a functional target of miRNA let-7a and acts as a tumor promoter in osteosarcoma.CBX2 是 miRNA let-7a 的一个功能靶标,在骨肉瘤中作为一种肿瘤促进因子发挥作用。
Cancer Med. 2019 Jul;8(8):3981-3991. doi: 10.1002/cam4.2320. Epub 2019 May 31.
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The role of mA RNA methylation in human cancer.mRNA 甲基化在人类癌症中的作用。
Mol Cancer. 2019 May 29;18(1):103. doi: 10.1186/s12943-019-1033-z.
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KIAA1429 regulates the migration and invasion of hepatocellular carcinoma by altering m6A modification of ID2 mRNA.KIAA1429通过改变ID2 mRNA的m6A修饰来调节肝细胞癌的迁移和侵袭。
Onco Targets Ther. 2019 May 7;12:3421-3428. doi: 10.2147/OTT.S180954. eCollection 2019.
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WT1 associated protein promotes metastasis and chemo-resistance to gemcitabine by stabilizing Fak mRNA in pancreatic cancer.WT1 相关蛋白通过稳定胰腺癌中 Fak mRNA 促进转移和吉西他滨耐药性。
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Long non-coding RNA PVT1 promotes tumor progression by regulating the miR-143/HK2 axis in gallbladder cancer.长链非编码 RNA PVT1 通过调控 miR-143/HK2 轴促进胆囊癌的进展。
Mol Cancer. 2019 Mar 2;18(1):33. doi: 10.1186/s12943-019-0947-9.
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m6A modification of non-coding RNA and the control of mammalian gene expression.非编码 RNA 的 m6A 修饰与哺乳动物基因表达的调控。
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KIAA1429 通过促进干细胞特性促进骨肉瘤的进展,并且受 miR-143-3p 调控。

KIAA1429 promotes osteosarcoma progression by promoting stem cell properties and is regulated by miR-143-3p.

机构信息

Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Bone and Soft Tissue, Zhengzhou Central Affiliated Hospital to Zhengzhou University, Zhengzhou, China.

出版信息

Cell Cycle. 2020 May;19(10):1172-1185. doi: 10.1080/15384101.2020.1749465. Epub 2020 Apr 14.

DOI:10.1080/15384101.2020.1749465
PMID:32286148
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7217356/
Abstract

: Osteosarcoma (OS) is the most common primary bone malignancy, it has a dismal prognosis and mainly affects the children and adolescents. Previous reports have demonstrated that aberrantly expressed KIAA1429 plays crucial roles in the carcinogenesis of several cancers, but its expression status and functional role in the progression of OS have not previously been investigated.: Immunohistochemistry (IHC) and western blotting were conducted to determine KIAA1429 expression status in OS. The relationship between KIAA1429 expression and OS prognosis was analyzed based on public database and tissue microarray (TMA). Cell proliferation ability was evaluated by CCK8, EdU and colony formation assays, and Transwell and wound healing potential were also assessed . Xenograft nude mouse model was performed to elucidate the tumor growth . The main specific miRNA targeting KIAA1429 in OS cells was identified.: KIAA1429 expression is markedly overexpressed in OS, and elevated KIAA1429 expression is significantly associated with an unfavorable prognosis. Functional investigations demonstrate that KIAA1429 silencing could attenuate proliferation, migration and invasion abilities of OS , as well as tumor growth . Mechanistically, microRNA-143-3p (miR-143-3p) was identified as the crucial specific mediator of KIAA1429 expression in OS cells. Furthermore, restoring KIAA1429 expression could partially reverse miR-143-3p mediated tumor-inhibition effects. Additionally, we found that knockdown of KIAA1429 or ectopic overexpression of miR-143-3p could repress stemness cell properties and the inhibition could be partly abolished by overexpression of KIAA1429.: In summary, this study establishes miR-143-3p/KIAA1429 axis as promising therapeutic target for OS patients.

摘要

骨肉瘤(OS)是最常见的原发性骨恶性肿瘤,预后不良,主要影响儿童和青少年。先前的报告表明,异常表达的 KIAA1429 在几种癌症的发生中起着关键作用,但它在 OS 进展中的表达状态和功能作用尚未被研究过。

免疫组织化学(IHC)和 Western blot 用于确定 OS 中 KIAA1429 的表达状态。根据公共数据库和组织微阵列(TMA)分析 KIAA1429 表达与 OS 预后的关系。通过 CCK8、EdU 和集落形成测定评估细胞增殖能力,还评估了 Transwell 和伤口愈合潜力。进行异种移植裸鼠模型以阐明肿瘤生长。确定 OS 细胞中针对 KIAA1429 的主要特定 miRNA。

KIAA1429 在 OS 中表达明显过表达,并且升高的 KIAA1429 表达与不良预后显著相关。功能研究表明,KIAA1429 沉默可减弱 OS 中增殖、迁移和侵袭能力以及肿瘤生长。机制上,microRNA-143-3p(miR-143-3p)被鉴定为 OS 细胞中 KIAA1429 表达的关键特异性介质。此外,恢复 KIAA1429 表达可部分逆转 miR-143-3p 介导的肿瘤抑制作用。此外,我们发现下调 KIAA1429 或过表达 miR-143-3p 可抑制干细胞特性,而过表达 KIAA1429 可部分消除抑制作用。

总之,本研究确立了 miR-143-3p/KIAA1429 轴作为骨肉瘤患者有前途的治疗靶点。