Department of Oral Pathology, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of Korea.
Department of Biochemistry, Chonnam National University Medical School, Hwasun 58128, Republic of Korea.
Genes (Basel). 2023 Aug 28;14(9):1709. doi: 10.3390/genes14091709.
Fibrolamellar carcinoma (FLC) is a rare type of liver cancer that primarily affects adolescents and young adults without prior liver disease or viral infections. Patients with FLC generally have non-specific symptoms, are often diagnosed at a later stage, and experience a higher frequency of metastases compared to patients with other liver cancers. A fusion transcript of DNAJB1 and PRKACA, which can lead to increased activity of PKA and cellular proliferation, has been identified in all FLC patients, but the exact mechanism through which FLC develops remains unclear. In this study, we investigated common lncRNA profiles in various FLC samples using bioinformatics analyses.
We analyzed differentially expressed (DE) lncRNAs from three RNA sequencing datasets. Using lncRNAs and DE mRNAs, we predicted potential lncRNA target genes and performed Gene Ontology (GO) and KEGG analyses with the DE lncRNA target genes. Moreover, we screened for small-molecule compounds that could act as therapeutic targets for FLC.
We identified 308 DE lncRNAs from the RNA sequencing datasets. In addition, we performed a trans-target prediction analysis and identified 454 co-expressed pairs in FLC. The GO analysis showed that the lncRNA-related up-regulated mRNAs were enriched in the regulation of protein kinase C signaling and cAMP catabolic processes, while lncRNA-related down-regulated mRNAs were enriched in steroid, retinol, cholesterol, and xenobiotic metabolic processes. The analysis of small-molecule compounds for FLC treatment identified vitexin, chlorthalidone, triamterene, and amiloride, among other compounds.
We identified potential therapeutic targets for FLC, including lncRNA target genes as well as small-molecule compounds that could potentially be used as treatments. Our findings could contribute to furthering our understanding of FLC and providing potential avenues for diagnosis and treatment.
纤维板层样肝癌（FLC）是一种罕见的肝癌，主要影响青少年和年轻成年人，且无先前的肝脏疾病或病毒感染。FLC 患者通常具有非特异性症状，往往在晚期被诊断出来，并且比其他肝癌患者更容易发生转移。在所有 FLC 患者中都发现了 DNAJB1 和 PRKACA 的融合转录本，这可能导致 PKA 的活性增加和细胞增殖，但是 FLC 发展的确切机制尚不清楚。在这项研究中，我们使用生物信息学分析方法研究了各种 FLC 样本中的常见 lncRNA 图谱。
我们分析了来自三个 RNA 测序数据集的差异表达（DE）lncRNA。使用 lncRNA 和 DE mRNA，我们预测了潜在的 lncRNA 靶基因，并对 DE lncRNA 靶基因进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析。此外，我们筛选了可作为 FLC 治疗靶点的小分子化合物。
我们从 RNA 测序数据集中鉴定出 308 个 DE lncRNA。此外，我们进行了转靶预测分析，在 FLC 中鉴定出 454 个共表达对。GO 分析表明，lncRNA 相关上调的 mRNAs 富集在蛋白激酶 C 信号和 cAMP 分解代谢过程的调节中，而 lncRNA 相关下调的 mRNAs 富集在类固醇、视黄醇、胆固醇和异生物代谢过程中。用于 FLC 治疗的小分子化合物分析鉴定出了牡荆素、氯噻酮、三氨蝶呤和阿米洛利等化合物。
我们鉴定出了 FLC 的潜在治疗靶点，包括 lncRNA 靶基因以及可能用作治疗方法的小分子化合物。我们的研究结果可能有助于进一步了解 FLC，并为诊断和治疗提供潜在途径。
