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目的:筛选与非小细胞肺癌(NSCLC)转移相关的microRNAs,为研究其在转移过程中发挥的作用提供理论基础。方法:用荧光转染的人NSCLC细胞株H460皮下成瘤后原位移植于裸鼠左肺获取原发灶与转移灶组织标本。通过mi-croRNA芯片检测和RT-PCR验证筛选与转移相关的差异microRNAs,并对其做生物信息学分析。结果:NSCLC有转移原发灶比无转移原发灶(A组)上调的microR-NAs共17个,下调的7个;转移灶比转移原发灶(B组)上调的microRNAs共20个,下调的16个。A组中表达上调的有miR-10b和miR-144,下调的有miR-9、miR-31和miR-34b;B组中表达下调的有miR-25、miR-92a、miR-202和miR-326,它们可能受转录因子AP-1、p53、STATs和NF-κB等调控,作用于RARβ、RASSF1和E2F-1等靶基因,发挥调控细胞增殖周期、细胞发育过程、DNA和RNA代谢及信号传导通路的作用,促进肿瘤生长和转移。结论:在NSCLC有转移和无转移组织中microRNA的表达谱存在差异,它们通过多种途径对肿瘤细胞的增殖、黏附、迁移和浸润起调控作用。
Objective: To screen microRNAs related to non-small cell lung cancer (NSCLC) metastasis and provide the theoretical basis for studying its role in metastasis. Methods: Human NSCLC cell line H460 transfected with fluorescence was subcutaneously transplanted in the left lung of nude mice in situ to obtain primary and metastatic tissue samples. Differentiated microRNAs related to metastasis were screened by mi-croRNA microarray and RT-PCR, and their bioinformatics analysis was performed. Results: A total of 17 microRNAs were upregulated in NSCLC compared with those without metastasis (group A), and 17 were down-regulated. Twenty microRNAs were upregulated in metastasis compared with those in primary metastasis (group B) Down 16. MiR-10b and miR-144 were upregulated in group A, and miR-9, miR-31 and miR-34b were down-regulated in group A; miR-25, miR-92a, miR- -326, which may be regulated by the transcription factors AP-1, p53, STATs and NF-κB and play a role in target genes such as RARβ, RASSF1 and E2F-1 to regulate cell cycle, cell development, DNA and RNA metabolism and The role of signaling pathways to promote tumor growth and metastasis. Conclusion: The expression patterns of microRNAs in NSCLC with metastasis and metastasis are different. They regulate the proliferation, adhesion, migration and invasion of tumor cells in many ways.