Effect of MALAT1 Polymorphisms on Papillary Thyroid Cancer in a Chinese Population
Effect of MALAT1 Polymorphisms on Papillary Thyroid Cancer in a Chinese Population
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MALAT1 多态性对中国人群甲状腺乳头状癌的影响
DOI：
10.7150/jca.28887
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发表时间：
2019-01-01
影响因子：
3.9
通讯作者：
Shi, Lixin
中科院分区：
文献类型：
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作者：
Wen, Jing;Chen, Liang;Shi, Lixin
背景：长链非编码RNA MALAT1先前已被报道与多种肿瘤的致癌作用有关，其潜在的功能多态性也在多种疾病中得到了研究。然而，这些多态性与甲状腺癌易感性之间的关系仍不清楚。在本研究中，我们旨在探讨MALAT1多态性与甲状腺癌（TC）易感性之间的关联，以及TC中潜在的生物学功能。方法：我们对1134例甲状腺乳头状癌（PTC）患者和1228例对照进行了病例对照研究，以评估MALAT1遗传变异（单核苷酸多态性，SNP）与PTC风险之间的潜在相关性。通过荧光素酶测定、细胞计数试剂盒8（CCK-8）和流式细胞术探索更详细的分子机制。结果：MALAT1 SNP rs619586被确定为PTC易感性的显着保护因素（P = 0.017，OR = 0.76，95％CI = 0.60-0.95）。 rs619586的进一步功能实验表明，rs619586的G等位基因可以显着降低MALAT1表达，减少PTC增殖，并直接增加PTC凋亡。结论：我们的研究结果表明，MALAT1 SNP rs619586可以作为PTC易感性和发病机制的潜在指标。
Background: Long noncoding RNA MALAT1 has been previously reported in the carcinogenesis of several tumors, and its potential functional polymorphisms have also been investigated in various diseases. However, the relationship between these polymorphisms and the susceptibility of thyroid cancer has still been largely unknown. In the present study, we aimed to explore the association between MALAT1 polymorphisms and thyroid cancer (TC) susceptibility, as well as potential biological function in TC.Methods: We conducted a case-control study with 1134 papillary thyroid cancer (PTC) patients and 1228 controls to evaluate the potential correlation between MALAT1 genetic variations (single nucleotide polymorphism, SNP) and the risk of PTC. More detailed molecular mechanisms were explored by luciferase assay, cell counting kit-8 (CCK-8), and flow cytometry.Results: MALAT1 SNP rs619586 was identified as a significantly protective factor of PTC susceptibility (P = 0.017, OR= 0.76, 95%CI = 0.60-0.95). Further functional experiments of rs619586 indicated that G allele of rs619586 could significantly decrease MALAT1 expression, reduce PTC proliferation, and directly increase PTC apoptosis.Conclusions: Our findings suggested that MALAT1 SNP rs619586 could serve as a potential indicator for PTC susceptibility and pathogenesis.