Biomedical Research Center, the Affiliated Calmette Hospital of Kunming Medical University (the First Hospital of Kunming), No. 504 Qingnian Road, Kunming, 650011, Yunnan, China.
Department of Anesthesiology, the First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China.
Respir Res. 2018 Jun 11;19(1):115. doi: 10.1186/s12931-018-0819-7.
Lung cancer had been leading mounts of deaths worldwide. Advances in genes microarray had helped human further understand genes and identify novel circular RNAs. This study aimed at investigating the biological functions and molecular mechanisms of hsa_circ_0046264 in lung cancer which may be helpful in lung cancer early diagnosis and clinical treatment.
Gene microarray data screened the differential gene of hsa_circ_0046264 and its downstream genes were found by bioinformatics analysis and verified by luciferase reporter assay. QRT-PCR and Western blot was used to detect the RNA and protein levels respectively. RNase R digestion confirmed the existences of circular RNA. Cell viability, invasion and apoptosis were determined by MTT assay, flow cytometry and DNA damage assay. Tumor formation in nude mice and immunohistochemistry proved the functions of hsa_circ_0046264 in vivo.
Hsa_circ_0046264 and BRCA2 were down-regulated in lung cancer tissues while miR-1245 was up-regulated. Hsa_circ_0046264 induced apoptosis but inhibited proliferation and invasion of lung cancer cells through targeting miR-1245 to up-regulate BRCA2. Hsa_circ_0046264 inhibited the tumor growth in vivo.
Hsa_circ_0046264 was a tumor suppressor in lung cancer. Overexpression of hsa_circ_0046264 could up-regulate BRCA2 expression through down-regulating of miR-1245.
肺癌是全球导致死亡人数最多的疾病。基因芯片技术的进步帮助人类进一步了解基因，并鉴定出新型环状 RNA。本研究旨在探讨 hsa_circ_0046264 在肺癌中的生物学功能和分子机制，这可能有助于肺癌的早期诊断和临床治疗。
通过基因芯片数据分析筛选 hsa_circ_0046264 的差异基因，通过生物信息学分析找到其下游基因，并通过荧光素酶报告基因实验进行验证。实时定量聚合酶链反应（QRT-PCR）和 Western blot 分别用于检测 RNA 和蛋白质水平。用 RNase R 消化实验验证环状 RNA 的存在。通过 MTT 检测、流式细胞术和 DNA 损伤检测分别检测细胞活力、侵袭和凋亡。裸鼠肿瘤形成和免疫组织化学证实了 hsa_circ_0046264 在体内的功能。
hsa_circ_0046264 和 BRCA2 在肺癌组织中下调，而 miR-1245 上调。hsa_circ_0046264 通过靶向 miR-1245 上调 BRCA2 诱导肺癌细胞凋亡，但抑制增殖和侵袭。hsa_circ_0046264 抑制体内肿瘤生长。
hsa_circ_0046264 是肺癌的肿瘤抑制因子。hsa_circ_0046264 的过表达可通过下调 miR-1245 来上调 BRCA2 的表达。
