Abstract：
BACKGROUND: Lung adenocarcinoma (LUAD) is a major health challenge worldwide with an undesirable prognosis. LINC00982 has been implicated as a tumor suppressor in diverse human cancers; however, its role in LUAD has not been fully characterized.
METHODS: Expression level and prognostic value of LINC00982 were investigated in pan-cancer and lung cancer from The Cancer Genome Atlas (TCGA) project. Differential expression analysis based on the LINC00982 expression level was performed in LUAD followed by gene set enrichment analysis (GSEA) and functional enrichment analyses. The association between LINC00982 expression and tumor immune microenvironment characteristics was evaluated. A potential ceRNA regulatory axis was identified and experimentally validated.
RESULTS: We found that LINC00982 expression was downregulated and correlated with poor prognosis in LUAD. Enrichment analyses revealed that LINC00982 could inhibit DNA damage repair and cell proliferation, but enhance tumor metabolic reprogramming. We identified a competing endogenous RNA network involving LINC00982, miR-183-5p, and ATP-binding cassette subfamily A member 8 (ABCA8). Luciferase assays confirmed that miR-183-5p can interact with LINC00982 and ABCA8. Forced miR-183-5p expression reduced LINC00982 transcript levels and suppressed ABCA8 expression.
CONCLUSIONS: Our findings revealed the LINC00982/miR-183-5p/ABCA8 axis as a potential therapeutic target in LUAD.
METHODS: Expression level and prognostic value of LINC00982 were investigated in pan-cancer and lung cancer from The Cancer Genome Atlas (TCGA) project. Differential expression analysis based on the LINC00982 expression level was performed in LUAD followed by gene set enrichment analysis (GSEA) and functional enrichment analyses. The association between LINC00982 expression and tumor immune microenvironment characteristics was evaluated. A potential ceRNA regulatory axis was identified and experimentally validated.
RESULTS: We found that LINC00982 expression was downregulated and correlated with poor prognosis in LUAD. Enrichment analyses revealed that LINC00982 could inhibit DNA damage repair and cell proliferation, but enhance tumor metabolic reprogramming. We identified a competing endogenous RNA network involving LINC00982, miR-183-5p, and ATP-binding cassette subfamily A member 8 (ABCA8). Luciferase assays confirmed that miR-183-5p can interact with LINC00982 and ABCA8. Forced miR-183-5p expression reduced LINC00982 transcript levels and suppressed ABCA8 expression.
CONCLUSIONS: Our findings revealed the LINC00982/miR-183-5p/ABCA8 axis as a potential therapeutic target in LUAD.
摘要：
背景：肺腺癌（LUAD）是全球范围内的主要健康挑战，预后不良。LINC00982被认为是多种人类癌症的肿瘤抑制因子；然而，其在LUAD中的作用尚未得到充分表征。
方法：从癌症基因组图谱（TCGA）项目中研究了LINC00982在泛癌症和肺癌中的表达水平和预后价值。在LUAD中进行基于LINC00982表达水平的差异表达分析,随后进行基因集富集分析(GSEA)和功能富集分析。评估了LINC00982表达与肿瘤免疫微环境特征之间的关联。鉴定并实验验证了潜在的ceRNA调节轴。
结果：我们发现LINC00982表达下调，并且与LUAD的不良预后相关。富集分析表明，LINC00982可以抑制DNA损伤修复和细胞增殖，而是增强肿瘤代谢重编程。我们确定了一个竞争性的内源性RNA网络，涉及LINC00982，miR-183-5p，和ATP结合盒亚家族A成员8(ABCA8)。荧光素酶测定证实miR-183-5p可以与LINC00982和ABCA8相互作用。强制miR-183-5p表达降低LINC00982转录物水平并抑制ABCA8表达。
结论：我们的发现揭示了LINC00982/miR-183-5p/ABCA8轴作为LUAD的潜在治疗靶点。
方法：从癌症基因组图谱（TCGA）项目中研究了LINC00982在泛癌症和肺癌中的表达水平和预后价值。在LUAD中进行基于LINC00982表达水平的差异表达分析,随后进行基因集富集分析(GSEA)和功能富集分析。评估了LINC00982表达与肿瘤免疫微环境特征之间的关联。鉴定并实验验证了潜在的ceRNA调节轴。
结果：我们发现LINC00982表达下调，并且与LUAD的不良预后相关。富集分析表明，LINC00982可以抑制DNA损伤修复和细胞增殖，而是增强肿瘤代谢重编程。我们确定了一个竞争性的内源性RNA网络，涉及LINC00982，miR-183-5p，和ATP结合盒亚家族A成员8(ABCA8)。荧光素酶测定证实miR-183-5p可以与LINC00982和ABCA8相互作用。强制miR-183-5p表达降低LINC00982转录物水平并抑制ABCA8表达。
结论：我们的发现揭示了LINC00982/miR-183-5p/ABCA8轴作为LUAD的潜在治疗靶点。
