Guan Guofang, Li Ranwei, Tang Wenfang, Liu Tiecheng, Su Zhenzhong, Wang Yan, Tan Jingjin, Jiang Shan, Wang Ke
2 Department of Otolaryngology, The Second Affiliated Hospital of Jilin University, Changchun, China.
3 Department of Urinary Surgery, The Second Affiliated Hospital of Jilin University, Changchun, China.
Tumour Biol. 2017 Mar;39(3):1010428317691740. doi: 10.1177/1010428317691740.
This study assessed RNA-binding motif 10 expression in lung adenocarcinoma tissues and examined the role and mechanism of RNA-binding motif 10 in the regulation of lung adenocarcinoma malignancy. Lung adenocarcinoma and corresponding adjacent non-tumor lung tissues from 41 patients were subjected to reverse transcription-polymerase chain reaction and Western blot assessment to detect RNA-binding motif 10 expression. Recombinant lentivirus carrying RNA-binding motif 10 complementary DNA was used to infect lung adenocarcinoma cell lines, A549 and H1299 cells. Complementary DNA microarray was used to profile RNA-binding motif 10-regulated genes. Levels of RNA-binding motif 10 messenger RNA and protein were significantly lower in lung adenocarcinoma tissues than those in paired non-tumor tissues (p < 0.001). Reduced RNA-binding motif 10 expression was found to be associated with an advanced tumor stage. RNA-binding motif 10 overexpression inhibited viability and colony formation capacity of lung adenocarcinoma cell lines and induced cell-cycle arrest at G0/G1 phase in A549 cells and at S phase in H1299 cells. Complementary DNA microarray analysis identified 304 upregulated and 386 downregulated genes induced by RNA-binding motif 10 overexpression, which may be involved in cancer, focal adhesion, peroxisome proliferator-activated receptor-regulated gene pathway, cytokine-cytokine receptor interaction, mitogen-activated protein kinase signaling, complement and coagulation cascades, platelet amyloid precursor protein pathway, extracellular matrix-receptor interaction, and small cell lung cancer-related genes. Expression of FGF2, EGFR, WNT5A, NF-κB, and RAP1A was downregulated, whereas expression of AKT2, BIRC3, and JUN was upregulated. RNA-binding motif 10 messenger RNA and protein were reduced in lung adenocarcinoma tissues, and RNA-binding motif 10 overexpression inhibited lung adenocarcinoma cancer cell malignant behavior in vitro. Molecularly, RNA-binding motif 10 regulates many gene pathways involving in the tumor development or progression.
本研究评估了RNA结合基序10在肺腺癌组织中的表达,并探讨了RNA结合基序10在调控肺腺癌恶性程度中的作用及机制。对41例患者的肺腺癌组织及相应的癌旁非肿瘤肺组织进行逆转录-聚合酶链反应和蛋白质免疫印迹分析,以检测RNA结合基序10的表达。使用携带RNA结合基序10互补DNA的重组慢病毒感染肺腺癌细胞系A549和H1299细胞。采用互补DNA微阵列分析RNA结合基序10调控的基因。肺腺癌组织中RNA结合基序10信使核糖核酸和蛋白质水平显著低于配对的非肿瘤组织(p<0.001)。RNA结合基序10表达降低与肿瘤分期进展相关。RNA结合基序10过表达抑制了肺腺癌细胞系的活力和集落形成能力,并诱导A549细胞在G0/G1期、H1299细胞在S期发生细胞周期阻滞。互补DNA微阵列分析鉴定出RNA结合基序10过表达诱导的304个上调基因和386个下调基因,这些基因可能参与癌症、粘着斑、过氧化物酶体增殖物激活受体调控基因途径、细胞因子-细胞因子受体相互作用、丝裂原活化蛋白激酶信号传导、补体和凝血级联反应、血小板淀粉样前体蛋白途径、细胞外基质-受体相互作用以及小细胞肺癌相关基因。成纤维细胞生长因子2、表皮生长因子受体、WNT5A、核因子κB和RAP1A表达下调,而蛋白激酶B2、杆状病毒IAP重复序列3和原癌基因JUN表达上调。肺腺癌组织中RNA结合基序10信使核糖核酸和蛋白质减少,RNA结合基序10过表达在体外抑制肺腺癌细胞的恶性行为。在分子水平上RNA结合基序10调控许多参与肿瘤发生或进展过程的基因途径。