Annotation and cluster analysis of long noncoding RNA linked to male sex and estrogen in cancers
Annotation and cluster analysis of long noncoding RNA linked to male sex and estrogen in cancers
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癌症中与男性和雌激素相关的长非编码RNA的注释和聚类分析
DOI：
10.1038/s41698-020-0110-5
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发表时间：
2020-03-03
影响因子：
7.9
通讯作者：
Tao, Yongguang
中科院分区：
文献类型：
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作者：
Liu, Shouping;Lai, Weiwei;Tao, Yongguang
癌症发生的性别差异是癌症流行病学的一贯发现。几种实体瘤，包括肺癌、结直肠癌、肝癌和肾癌，通常在男性中更常见。尽管性二型性归因于荷尔蒙或行为的差异，但在性别特定的癌症中，缺乏lncRNA功能的证据。在此，我们发现LINC00263是肺腺癌中表达最失调的基因之一，在肺腺癌、结直肠癌和肾癌中表达上调，尤其是在男性患者中表达高于女性。LINC00263是一种癌基因，通过与细胞质中的IKKα相互作用，促进p65转位进入细胞核，激活核因子-kappaB信号通路。LINC00263的表达与ESR1密切相关，雌激素治疗后LINC00263的表达降低。配体激活的内质网通过抑制核转录因子-kappaB的胞浆转位而抑制LINC00263的功能。雌激素对LINC00263的抑制作用表明其在男性和女性患者中的表达存在差异。我们的发现表明，LINC00263与男性和雌激素作为癌基因有关，这些发现可能有助于探索性别特异性癌症差异基因调控的机制。
The sex difference in cancer occurrence is a consistent finding in cancer epidemiology. Several solid tumors, including lung cancer, colorectal cancer, hepatic carcinoma, and renal carcinoma, are generally more common in males. Although sexual dimorphism is attributed to hormonal or behavioral differences, evidence for the function of lncRNA is lacking in sex-specific cancers. We show here that LINC00263 is one of the most dysregulated lncRNAs in lung adenocarcinomas and is upregulated in lung adenocarcinoma, colorectal cancer, and renal carcinoma, especially in male patients compared to females. LINC00263 functions as an oncogene by promoting translocation of p65 into the nucleus to activate the NF-kappa B-signaling pathway through interaction with IKK alpha in the cytoplasm. The expression of LINC00263 is strongly correlated with ESR1, and it is decreased after treatment with estrogen. Ligand-activated ER could inhibit the function of LINC00263 by inhibiting NF-kappa B from cytoplasmic translocation into the nucleus. The inhibitory effect of estrogen on LINC00263 indicates its differential expression in male and female patients. Our findings indicate that LINC00263 is linked to male sex and estrogen as an oncogene, and these findings might help in the exploration of the mechanisms of differential gene regulation in sex-specific cancers.