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甲状腺癌是常见的内分泌肿瘤,其发病率增长迅速[1]。90%以上的甲状腺癌为分化型甲状腺癌(differentiated thyroid cancer,DTC)[2],主要包括甲状腺乳头状癌(papillary thyroid carcinoma,PTC)和甲状腺滤泡状癌(follicular thyroid carcinoma,FTC)两种病理类型。DTC患者接受手术切除、131I消融和TSH抑制治疗后预后通常较好,绝大多数患者10年生存率可达85%以上。甲状腺未分化癌(anaplastic thyroid carcinoma,ATC)是恶性程度最高的甲状腺癌,约为3%,患者总生存率仅为3~5个月[3]。
甲状腺癌的发生发展与丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)/细胞外调节蛋白激酶(extracellular regulated protein kinases,ERK)通路和磷脂酰肌醇3-激酶(phosphatidylinositol-3-kinases,PI3K)/蛋白质丝氨酸苏氨酸激酶(protein-serine-threonine kinase,AKT)通路信号传导失调密切相关[4],某些基因遗传失调导致上述两条信号通路过度活化,使甲状腺癌细胞过度增殖、转移且不受控制。其中,BRAFV600E基因突变和RET/PTC等基因重排是最常见的遗传改变[4]。近年来,长链非编码RNA(long non-coding RNAs,LncRNAs)受到研究者的极大关注,越来越多的研究发现[5]LncRNA与甲状腺癌的发生发展密切相关,其可在转录、转录后以及表观遗传水平调控基因的表达,对甲状腺癌细胞的增殖、凋亡、侵袭、转移等方面具有重要的调节功能。这揭示了LncRNAs参与甲状腺癌的发生发展,可为甲状腺癌的分子诊断和判断预后提供新思路,为难治性甲状腺癌寻找治疗新靶点。现将LncRNAs在甲状腺癌中的最新研究进展综述如下。
长链非编码RNA在甲状腺癌中的研究进展
Research progress of long non-coding RNAs in thyroid cancer
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摘要: 甲状腺癌是近年来发病率快速增长的内分泌肿瘤。人类恶性肿瘤与环境因素密切相关,环境改变可诱导机体内某些致病基因发生变化,从而促进了疾病的发生。在对人类的基因转录组的研究过程中,发现了一类长度超过200个核苷酸的非编码RNA,即长链非编码RNA(LncRNAs),其通过调节基因表达参与细胞分化、增殖、凋亡、迁移和侵袭等肿瘤的发生发展。越来越多的研究发现LncRNAs与甲状腺癌关系密切,许多LncRNAs对甲状腺有致癌或抑癌作用,但其具体功能和作用机制尚不明确。笔者对LncRNAs在甲状腺癌中的最新研究进展进行综述,为探讨LncRNAs在甲状腺癌中的作用机制及其临床应用价值提供依据。Abstract: Thyroid cancer is an endocrine tumor with a rapid increase in prevalence in recent years. Human malignant tumors are closely related to environmental factors. Environmental changes can induce changes in certain pathogenic genes in the body, thus promoting the occurrence of diseases. A class of non-coding RNAs over 200 nucleotides in length, known as long non-coding RNAs(LncRNAs), has been found in human transcriptomes. LncRNAs are non-coding RNAs over 200 nucleotides in length that are involved in tumorigenesis, cell proliferation, proliferation, apoptosis, migration, and invasion by regulating gene expression. More and more studies have found that LncRNAs are closely related to thyroid cancer. Many LncRNAs have carcinogenic or tumor suppressive effects on the thyroid gland, but its function and mechanism are still unclear. This article reviews the recent research progress of LncRNAs in thyroid cancer, and provides a basis for exploring the mechanism of LncRNAs in thyroid cancer and its clinical application.
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Key words:
- RNA, long noncoding /
- Thyroid neoplasms /
- Biomarkers /
- Diagnosis /
- Prognosis
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