背景:肝癌(LC)是中国最常见的恶性肿瘤之一,死亡率很高,排在胃癌和食管癌之后的第三大死亡原因。LncRNAFAM83H-AS1已被证实在LC的进展中发挥关键作用。然而,具体机制有待进一步调查。
方法:进行定量实时PCR(qRT-PCR)以测量基因的转录水平。通过CCK8和集落形成测定确定增殖。进行Westernblot以检测相对蛋白表达。构建异种移植小鼠模型以研究LncRNAFAM83H-AS1对体内肿瘤生长和放射敏感性的影响。
结果:lncRNAFAM83H-AS1的水平在LC中显著升高。FAM83H-AS1的敲低抑制LC细胞增殖和集落存活分数。FAM83HAS1的缺失增加了LC细胞对4GyX射线辐射的敏感性。在异种移植模型中,放疗联合FAM83H-AS1沉默可显着降低肿瘤体积和重量。FAM83H的过表达逆转了FAM83H-AS1缺失对LC细胞增殖和集落存活分数的影响。此外,FAM83H的过表达也恢复了异种移植模型中FAM83H-AS1的敲低或辐射引起的肿瘤体积和重量减少。
结论:敲低lncRNAFAM83H-AS1抑制LC生长并增强LC的放射敏感性。它有可能成为LC治疗的有希望的靶标。
BACKGROUND: Liver cancer (LC) is one of China\'s most common malignant tumors, with a high mortality rate, ranking third leading cause of death after gastric and esophageal cancer. Recent patents propose the LncRNA FAM83H-AS1 has been verified to perform a crucial role in the progression of LC. LncRNA FAM83H-AS1 has been verified to perform a crucial role in the progression of LC. However, the concrete mechanism remains to be pending further investigation.
OBJECTIVE: This study aimed to explore the embedding mechanism of FAM83H-AS1 molecules in terms of radio sensitivity of LC and provide potentially effective therapeutic targets for LC therapy.
METHODS: Quantitative real-time PCR (qRT-PCR) was conducted to measure the transcription levels of genes. Proliferation was determined via CCK8 and colony formation assays. Western blot was carried out to detect the relative protein expression. A xenograft mouse model was constructed to investigate the effect of LncRNA FAM83H-AS1 on tumor growth and radio-sensitivity in vivo.
RESULTS: The levels of lncRNA FAM83H-AS1 were remarkably increased in LC. Knockdown of FAM83H-AS1 inhibited LC cell proliferation and colony survival fraction. Deletion of FAM83H-AS1 increased the sensitivity of LC cells to 4 Gy of X-ray radiation. In the xenograft model, radiotherapy combined with FAM83H-AS1 silencing significantly reduced tumor volume and weight. Overexpression of FAM83H reversed the effects of FAM83H-AS1 deletion on proliferation and colony survival fraction in LC cells. Moreover, the over-expressing of FAM83H also restored the tumor volume and weight reduction caused by the knockdown of FAM83H-AS1 or radiation in the xenograft model.
CONCLUSIONS: Knockdown of lncRNA FAM83H-AS1 inhibited LC growth and enhanced radiosensitivity in LC. It has the potential to be a promising target for LC therapy.