Lung cancer is the most affected malignant tumor in the world, and its specific pathogenesis is still unclear. It has been confirmed that circ0001320 is down-regulated in lung cancer, but its mechanism has not been reported. Further study found that circ0001320 was down-regulated in lung cancer cells, localized in the cytoplasm, and had multiple miR-558 binding sites. Dual-luciferase reporter gene assay, RNA-pull-down, and immunoprecipitation experiments all confirmed that circ0001320 directly bound to miR-558, and then inhibit the expression of miR-558. MiR-558 was up-regulated in lung cancer cells, and bound the downstream target genes TNFAIP1 and TPM1 to inhibit their expression. Western blot showed that circ0001320 significantly up-regulated the protein levels of TNFAIP1 and TPM1, while miR-558 blocked this effect of circ0001320. Circ0001320, TNFAIP1, and TPM1 all inhibited the proliferation and invasion of lung cancer cells and promoted apoptosis, while miR-558 had the opposite effects. After transfection with circ0001320 overexpression vector, miR-558 up-regulation or down-regulation of TNFAIP1, or TPM1 expression significantly reversed the inhibition of cell growth and invasion by circ0001320. Similarly, the expression of TNFAIP1 or TPM1 was down-regulated, while miR-558 expression was inhibited, and the levels of cell proliferation, apoptosis, and invasion did not change significantly. Therefore, these fully show that circ0001320 inhibits the growth and invasion of lung cancer cells through miR-558/TNFAIP1 and TPM1 pathways, which may be closely related markers and therapeutic targets of lung cancer.

肺癌是世界上影响最大的恶性肿瘤，其具体发病机制尚不清楚。circ0001320在肺癌中被证实下调，但其机制尚未见报道。进一步研究发现circ0001320在肺癌细胞中下调，定位于细胞质中，具有多个miR-558结合位点。双荧光素酶报告基因检测、RNA-pull-down和免疫沉淀实验均证实circ0001320直接与miR-558结合，进而抑制miR-558的表达。MiR-558 在肺癌细胞中上调，并结合下游靶基因 TNFAIP1 和 TPM1 抑制它们的表达。蛋白质印迹显示 circ0001320 显着上调 TNFAIP1 和 TPM1 的蛋白质水平，而 miR-558 阻断了 circ0001320 的这种作用。Circ0001320, TNFAIP1、TPM1均抑制肺癌细胞的增殖和侵袭，促进细胞凋亡，而miR-558则相反。用circ0001320过表达载体转染后，miR-558上调或下调TNFAIP1或TPM1表达显着逆转了circ0001320对细胞生长和侵袭的抑制。同样，TNFAIP1或TPM1的表达下调，而miR-558的表达受到抑制，细胞增殖、凋亡和侵袭水平无明显变化。因此，这些充分表明circ0001320通过miR-558/TNFAIP1和TPM1通路抑制肺癌细胞的生长和侵袭，这可能是肺癌密切相关的标志物和治疗靶点。和TPM1均抑制肺癌细胞的增殖和侵袭，促进细胞凋亡，而miR-558则具有相反的作用。用circ0001320过表达载体转染后，miR-558上调或下调TNFAIP1或TPM1表达显着逆转了circ0001320对细胞生长和侵袭的抑制。同样，TNFAIP1或TPM1的表达下调，而miR-558的表达受到抑制，细胞增殖、凋亡和侵袭水平无明显变化。因此，这些充分表明circ0001320通过miR-558/TNFAIP1和TPM1通路抑制肺癌细胞的生长和侵袭，这可能是肺癌密切相关的标志物和治疗靶点。和TPM1均抑制肺癌细胞的增殖和侵袭，促进细胞凋亡，而miR-558则具有相反的作用。用circ0001320过表达载体转染后，miR-558上调或下调TNFAIP1或TPM1表达显着逆转了circ0001320对细胞生长和侵袭的抑制。同样，TNFAIP1或TPM1的表达下调，而miR-558的表达受到抑制，细胞增殖、凋亡和侵袭水平无明显变化。因此，这些充分表明circ0001320通过miR-558/TNFAIP1和TPM1通路抑制肺癌细胞的生长和侵袭，这可能是肺癌密切相关的标志物和治疗靶点。用circ0001320过表达载体转染后，miR-558上调或下调TNFAIP1或TPM1表达显着逆转了circ0001320对细胞生长和侵袭的抑制。同样，TNFAIP1或TPM1的表达下调，而miR-558的表达受到抑制，细胞增殖、凋亡和侵袭水平无明显变化。因此，这些充分表明circ0001320通过miR-558/TNFAIP1和TPM1通路抑制肺癌细胞的生长和侵袭，这可能是肺癌密切相关的标志物和治疗靶点。用circ0001320过表达载体转染后，miR-558上调或下调TNFAIP1或TPM1表达显着逆转了circ0001320对细胞生长和侵袭的抑制。同样，TNFAIP1或TPM1的表达下调，而miR-558的表达受到抑制，细胞增殖、凋亡和侵袭水平无明显变化。因此，这些充分表明circ0001320通过miR-558/TNFAIP1和TPM1通路抑制肺癌细胞的生长和侵袭，这可能是肺癌密切相关的标志物和治疗靶点。TNFAIP1或TPM1表达下调，而miR-558表达受到抑制，细胞增殖、凋亡、侵袭水平无明显变化。因此，这些充分表明circ0001320通过miR-558/TNFAIP1和TPM1通路抑制肺癌细胞的生长和侵袭，这可能是肺癌密切相关的标志物和治疗靶点。TNFAIP1或TPM1表达下调，而miR-558表达受到抑制，细胞增殖、凋亡、侵袭水平无明显变化。因此，这些充分表明circ0001320通过miR-558/TNFAIP1和TPM1通路抑制肺癌细胞的生长和侵袭，这可能是肺癌密切相关的标志物和治疗靶点。