circ-PRKCA通过竞争性结合miR-330调控HMGB3在非小细胞肺癌增殖和侵袭中的作用及机制研究

批准号:
82002455
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
廖鑫
依托单位:
学科分类:
肿瘤表观遗传
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
廖鑫
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中文摘要
肺癌是最常见、病死率最高的恶性肿瘤,以非小细胞肺癌(NSCLC)为主,严重威胁人类健康。当前综合治疗方案下,NSCLC的5年生存率仍低于20%,亟需探索新的诊治方法和靶点。新近发现环状RNA在多种肿瘤发生发展中扮演重要角色,是肿瘤诊治的潜在靶点,但其在NSCLC中的调控作用仍有待深入探索。我们以高通量测序结果为基础,分析30对肺癌和癌旁标本发现circ-PRCKA在NSCLC中表达显著上调,而敲低后能有效抑制肺癌细胞增殖和侵袭能力。进一步pulldown和结合位点突变证实circ-PRKCA能竞争性结合miR-330,抑制其对HMGB3 3’-UTR的调控,上调HMGB3表达,进而促进NSCLC进展。本课题拟在大量前期工作基础上,系统解析circ-PRKCA在NSCLC增殖和侵袭中的作用及分子机制。本项目有望首次揭示circ-PRKCA在NSCLC中的调控作用,为探索新的诊疗靶点提供思路。
英文摘要
Lung cancer is the most common malignant tumor and the leading cause of cancer-related deaths in the world. Among those, non-small cell lung cancer (NSCLC) represents 80-90% of lung cancer cases. Although much effort has been made to improve the treatment of NSCLC, the prognosis remains poor and the 5-year survival rate is still less than 20%. Thus exploring new therapeutic targets is urgently needed. In recent years, circular RNAs have been shown to play significant roles in different tumors. So they are expected to become new breakthrough in tumor therapy. However, the expression patterns and clinical implications of circRNAs in NSCLC remain obscure. Our previous study found that the expression of circ-PRKCA was dramatically over-expressed in NSCLC as compared with normal tissues, and sh-circ-PRKCA could remarkable inhibit the proliferation and invasion of NSCLC cells. Further study showed that circ-PRKCA could bind to miR-330-5p competing with HMGB3 3’-UTR, consequently up-regulate the expression of HMGB3 and promote the progression of NSCLC. On these basis, this project tries to systemically reveal the detail mechanism underlying the regulation of circ-PRKCA in NSCLC proliferation and invasion. The successful conduct of this project is expected to reveal the function of circ-PRKCA in NSCLC progression and the molecular mechanism, consequently providing new ideas for diagnosis and treatment of NSCLC.
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DOI:10.1038/s41419-023-06373-z
发表时间:2024-01-05
期刊:CELL DEATH & DISEASE
影响因子:9
作者:Shuai, Yujun;Zhang, Hui;Liu, Changhao;Wang, Junting;Jiang, Yangkai;Sun, Jiayin;Gao, Xincheng;Bo, Xiaochen;Xiao, Xingyuan;Liao, Xin;Huang, Chao;Chen, Hebing;Jiang, Guosong
通讯作者:Jiang, Guosong
DOI:10.1002/ctm2.1546
发表时间:2024-01
期刊:Clinical and translational medicine
影响因子:10.6
作者:
通讯作者:
国内基金
海外基金
