Department of Biochemistry, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
Int J Mol Sci. 2020 Mar 9;21(5):1859. doi: 10.3390/ijms21051859.
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide. For patients who are resistant to monotherapy, multimodal therapy is a basic oncologic principle that incorporates surgery, radiotherapy (RT), and chemotherapy providing survival benefits for patients with most types of cancer. Although liver has low tolerance for radiation, high-precision RT for local HCC minimizes the likelihood of radiation-induced liver disease (RILD) in noncancerous liver tissue. RT have several therapeutic benefits, including the down-staging of tumors to make them resectable and repression of metastasis. The DNA damage response (DDR) is a cellular response to irradiation (IR), including DNA repair of injured cells and induction of programmed cell death, thereby resulting in maintenance of cell homeostasis. Molecules that block the activity of proteins in DDR pathways have been found to enhance radiotherapeutic effects. These molecules include antibodies, kinase inhibitors, siRNAs and miRNAs. MicroRNAs (miRNAs) are short non-coding regulatory RNAs binding to the 3'-untranslated regions (3'-UTR) of the messenger RNAs (mRNAs) of target genes, regulating their translation and expression of proteins. Thus, miRNAs and their target genes constitute complicated interactive networks, which interact with other molecules during carcinogenesis. Due to their promising roles in carcinogenesis, miRNAs were shown to be the potential factors that mediated radiosensitivity and optimized outcomes of the combination of systemic therapy and radiotherapy.
肝细胞癌（HCC）是全球癌症相关死亡的第四大主要原因。对于对单药治疗耐药的患者，多模式治疗是一种基本的肿瘤学原则，它将手术、放疗（RT）和化疗结合在一起，为大多数类型的癌症患者提供生存获益。尽管肝脏对辐射的耐受性较低，但针对局部 HCC 的高精度 RT 最大限度地降低了非癌性肝组织中辐射性肝病（RILD）的发生几率。RT 具有多种治疗益处，包括使肿瘤降级以使其可切除和抑制转移。DNA 损伤反应（DDR）是细胞对辐射（IR）的反应，包括受损细胞的 DNA 修复和程序性细胞死亡的诱导，从而维持细胞内稳态。已经发现阻断 DDR 途径中蛋白质活性的分子可以增强放射治疗效果。这些分子包括抗体、激酶抑制剂、siRNA 和 miRNA。miRNAs 是短的非编码调控 RNA，与靶基因的信使 RNA（mRNA）的 3'-非翻译区（3'-UTR）结合，调节其翻译和蛋白质的表达。因此，miRNAs 及其靶基因构成复杂的相互作用网络，在致癌过程中与其他分子相互作用。由于它们在致癌作用中具有很有前景的作用，因此 miRNAs 被证明是介导放射敏感性的潜在因素，并优化了系统治疗和放疗联合治疗的结果。
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