Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Changsari, 781101, Assam, India.
Life Sci. 2023 Jul 15;325:121751. doi: 10.1016/j.lfs.2023.121751. Epub 2023 May 9.
Hepatocellular carcinoma (HCC) is among the deadliest cancer in human malignancies. It is the most common and severe type of primary liver cancer. However, the molecular mechanisms underlying HCC pathogenesis remain poorly understood. Long non-coding RNAs (lncRNAs), a new kind of RNA and epigenetic factors, play a crucial role in tumorigenesis and the progression of HCC. LncRNAs are capable of promoting the autophagy, proliferation, and migration of tumor cells by targeting and modulating the expression of downstream genes in signaling pathways related to cancer; these transcripts modify the activity and expression of various tumor suppressors and oncogenes. LncRNAs could act as biomarkers for treatment approaches such as immunotherapy, chemotherapy, and surgery to effectively treat HCC patients. Improved knowledge regarding the aetiology of HCC may result from an advanced understanding of lncRNAs. Enhanced oxidative stress in the mitochondrial and Endoplasmic reticulum leads to the activation of unfolded protein response pathway that plays a crucial role in the pathophysiology of hepatocellular carcinoma. The mutual regulation between LncRNAs and Endoplasmic reticulum (ER) stress in cancer and simultaneous activation of the unfolded protein response (UPR) pathway determines the fate of tumor cells in HCC. Mitochondria-associated lncRNAs work as essential components of several gene regulatory networks; abnormal regulation of mitochondria-associated lncRNAs may lead to oncogenesis, which provides further insight into the understanding of tumorigenesis and therapeutic strategies.
肝细胞癌 (HCC) 是人类恶性肿瘤中最致命的癌症之一。它是原发性肝癌中最常见和最严重的类型。然而，HCC 发病机制的分子机制仍知之甚少。长链非编码 RNA（lncRNA）是一种新型 RNA 和表观遗传因子，在肿瘤发生和 HCC 的进展中起着关键作用。lncRNA 能够通过靶向和调节与癌症相关信号通路中下游基因的表达，促进肿瘤细胞的自噬、增殖和迁移；这些转录物修饰各种肿瘤抑制因子和癌基因的活性和表达。lncRNA 可以作为治疗方法的标志物，如免疫疗法、化疗和手术，以有效治疗 HCC 患者。对 lncRNA 的深入了解可能会导致对 HCC 病因的认识得到提高。
增强的线粒体和内质网中的氧化应激导致未折叠蛋白反应途径的激活，该途径在肝细胞癌的病理生理学中起着至关重要的作用。LncRNA 和内质网（ER）应激在癌症中的相互调节以及未折叠蛋白反应 (UPR) 途径的同时激活决定了 HCC 中肿瘤细胞的命运。与线粒体相关的 lncRNA 作为几个基因调控网络的重要组成部分；线粒体相关 lncRNA 的异常调节可能导致癌变，这为理解肿瘤发生和治疗策略提供了进一步的见解。
