Center for RNA Medicine, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark.
Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark.
Sci Rep. 2022 Nov 14;12(1):19502. doi: 10.1038/s41598-022-23802-9.
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer with increasing incidence in western countries. Most HCC patients have advanced cancer at the time of diagnosis due to the asymptomatic nature of early-stage HCC and do not qualify for potentially curative surgical treatment, thus, highlighting the need for new therapeutic strategies. Long noncoding RNAs (lncRNAs) comprise a large and heterogeneous group of non-protein coding transcripts that play important regulatory roles in numerous biological processes in cancer. In this study, we performed RNA sequencing of liver biopsies from ten HCC, ten hepatitis C virus-associated HCC, and four normal livers to identify dysregulated lncRNAs in HCC. We show that the lncRNA p53-upregulated-regulator-of-p53-levels (PURPL) is upregulated in HCC biopsies and that its expression is p53-dependent in liver cancer cell lines. In addition, antisense oligonucleotide-mediated knockdown of PURPL inhibited cell proliferation, induced apoptosis, and sensitized HepG2 human HCC cells to treatment with the chemotherapeutic agent doxorubicin. In summary, our findings suggest that PURPL could serve as a new therapeutic target for reversing doxorubicin resistance in HCC.
肝细胞癌 (HCC) 是最常见的原发性肝癌类型，其在西方国家的发病率呈上升趋势。由于早期 HCC 无症状，大多数 HCC 患者在诊断时已处于晚期癌症，不符合潜在治愈性手术治疗的条件，因此需要新的治疗策略。长链非编码 RNA (lncRNA) 是一大组异质的非蛋白编码转录物，在癌症中的许多生物学过程中发挥重要的调节作用。在这项研究中，我们对来自 10 例 HCC、10 例丙型肝炎病毒相关 HCC 和 4 例正常肝脏的肝活检组织进行了 RNA 测序，以鉴定 HCC 中失调的 lncRNA。我们表明，lncRNA p53 上调的 p53 水平调节因子 (PURPL) 在 HCC 活检组织中上调，并且其在肝癌细胞系中的表达依赖于 p53。此外，反义寡核苷酸介导的 PURPL 敲低抑制细胞增殖，诱导细胞凋亡，并使 HepG2 人 HCC 细胞对化疗药物阿霉素的治疗更敏感。总之，我们的研究结果表明，PURPL 可以作为逆转 HCC 中阿霉素耐药性的新治疗靶点。
