Circ0001320 inhibits lung cancer cell growth and invasion by regulating TNFAIP1 and TPM1 expression through sponging miR
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RESEARCH ARTICLE
Circ0001320 inhibits lung cancer cell growth and invasion by regulating TNFAIP1 and TPM1 expression through sponging miR‑558 Yong Mao1,3 · Jia‑xi He2 · Mei Zhu4 · Yong‑quan Dong5 · Jian‑xing He1,2 Received: 16 June 2020 / Accepted: 15 October 2020 © Japan Human Cell Society 2020
Abstract 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. Keywords Lung cancer · CircRNA · miR-558 · TNFAIP1 · TPM1
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13577-020-00453-4) contains supplementary material, which is available to authorized users. * Jian‑xing He [email protected] 1
The First Clinical College, Southern Medical University, No. 1023‑1063, Shatai South Road, Baiyun District, Guangzhou 510515, Guangdong, China
2
Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China
3
Department of Cardiothoracic Surgery, Ningbo First Hospital, Ningbo 315010, China
4
Ningbo University School of Medicine, Ningbo 315211, China
5
Department of Respiratory Disease, Yinzhou Second Hospital, Ningbo 315040, China
Lung cancer is a common malignant tumor which seriously threatens human health. It has become the first malignant tumor in incidence rate and mortality rate in China [1]. Therefore, to explore the biological characteristics and pathogenesis of lung cancer and to find the molecular markers for the diagnosis of lung c
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