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-κB-signaling pathway through interaction with IKKα 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-κB 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.

癌症发生的性别差异是癌症流行病学的一致发现。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。尽管性别二态性归因于激素或行为差异，但在性别特异性癌症中缺乏 lncRNA 功能的证据。我们在此表明​​ LINC00263 是肺腺癌中失调最严重的 lncRNA 之一，并且在肺腺癌、结直肠癌和肾癌中上调，尤其是在男性患者中与女性相比。LINC00263 通过与细胞质中的 IKKα 相互作用促进 p65 易位进入细胞核以激活 NF-κB 信号通路，从而起到致癌基因的作用。LINC00263 的表达与 ESR1 密切相关，并在用雌激素治疗后减少。配体激活的 ER 可以通过抑制 NF-κB 从细胞质易位进入细胞核来抑制 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差异。我们的研究结果表明，LINC00263 与男性和作为致癌基因的雌激素有关，这些发现可能有助于探索性别特异性癌症中差异基因调控的机制。