Circular RNA hsa_circ_0002483 promotes growth and invasion of lung adenocarcinoma by sponging miR-125a-3p

Wan, Jun; Ding, Guanggui; Zhou, Min; Ling, Xiean; Rao, Zhanpeng

2021-10-12

10.1186/s12935-021-02241-y

CANCER CELL INTERNATIONAL   影响因子和分区

1475-2867

Background Increasing evidence indicates that the aberrant expression of circular RNAs (circRNAs) is involved in the pathogenesis and progression of lung adenocarcinoma (LUAC). However, the function and molecular mechanisms of hsa_circ_0002483 (circ_0002483) in LUAC remain unclear. Methods The association between circ_0002483 expression and clinicopathological characteristics and prognosis in patients with LUAC was analyzed by fluorescence in situ hybridization. The functional experiments such as CCK-8, colony formation and Transwell assays and a subcutaneous tumor model were conducted to determine the role of circ_0002483 in LUAC cells. The specific binding between circ_0002483 and miR-125a-3p was validated by RNA immunoprecipitation, luciferase gene report and qRT-PCR assays. The effects of circ_0002483 on miR-125a-3p-mediated C-C motif chemokine ligand 4 (CCL4)-CCR5 axis were assessed by Western blot analysis. Results We found that circ_0002483 was upregulated in LUAC tissue samples and associated with Tumor Node Metastasis (TNM) stage and poor survival in patients with LUAC. Knockdown of circ_0002483 inhibited proliferation, colony formation and invasion of A549 and PC9 cells in vitro, whereas overexpression of circ_0002483 harbored the opposite effects. Furthermore, circ_0002483 sponged miR-125a-3p and negatively regulated its expression. CCL4 was identified as a direct target of miR-125a-3p. The rescue experiments showed that miR-125a-3p mimics reversed the tumor-promoting effects of circ_0002483 by targeting CCL4-CCR5 axis in A549 and PC9 cells. In addition, the in vivo experiment further validated that knockdown of circ_0002483 repressed tumor growth. Conclusions Our findings demonstrated that circ_0002483 could act as a sponge of miR-125a-3p to upregulate CCL4-CCR5 axis, contributing to the tumorigenesis of LUAC, and represent a potential therapeutic target for LUAC.

hsa_circ_0002483 miR-125a-3p Growth Invasion Lung adenocarcinoma

SCI

英语

第一 ; 通讯

Basic Research Project of Shenzhen Science and Technology Program (Natural Science Foundation)[JCYJ20190807144201675]

Oncology

Oncology

WOS:000707920300001

BMC

Web of Science

Southern Univ Sci & Technol, Jinan Univ, Affiliated Hosp 1, Shenzhen Peoples Hosp,Clin Med Coll 2,Dept Thorac, Shenzhen 518020, Peoples R China

Wan, Jun,Ding, Guanggui,Zhou, Min,et al. Circular RNA hsa_circ_0002483 promotes growth and invasion of lung adenocarcinoma by sponging miR-125a-3p[J]. CANCER CELL INTERNATIONAL,2021,21(1).

Wan, Jun,Ding, Guanggui,Zhou, Min,Ling, Xiean,&Rao, Zhanpeng.(2021).Circular RNA hsa_circ_0002483 promotes growth and invasion of lung adenocarcinoma by sponging miR-125a-3p.CANCER CELL INTERNATIONAL,21(1).

Wan, Jun,et al."Circular RNA hsa_circ_0002483 promotes growth and invasion of lung adenocarcinoma by sponging miR-125a-3p".CANCER CELL INTERNATIONAL 21.1(2021).