# Overexpression of hsa_circ_0061817 Can Inhibit the Proliferation and Invasion of Lung Cancer Cells Based on Active Compounds

**Authors:** Longping Ye, Youqing Zhong, Lihua Hu, Ya Huang, Xiang Tang, Shanjun Yu, Jianxin Huang, Ziyuan Wang, Qi Li, Xiangdong Zhou

PMC · DOI: 10.1155/2022/4509019 · 2022-09-16

## TL;DR

This study shows that overexpressing hsa_circ_0061817 reduces lung cancer cell growth and invasion, offering a potential new treatment target.

## Contribution

The novel finding is that hsa_circ_0061817 overexpression inhibits lung cancer progression by modulating EMT and apoptosis pathways.

## Key findings

- Overexpression of hsa_circ_0061817 significantly reduced cell viability, proliferation, and invasion in lung cancer cells.
- Hsa_circ_0061817 increased apoptosis and altered EMT-related protein expression in cancer cells.
- Hsa_circ_0061817 inhibited tumor growth in nude mice and may act via competitive binding to specific miRNAs.

## Abstract

This study was aimed at investigating the expression level of hsa_circ_0061817 in lung adenocarcinoma cells and its effect on cell proliferation and invasion and the possible mechanism of hsa_circ_0061817 in lung adenocarcinoma.

The overexpression plasmids of hsa_circ_0061817 (OE-hsacirc_0061817) were transfected into human lung A549 cells and mouse LLC-LUC cells, respectively. The cell viability was detected by CCK-8, and the cell proliferation was detected by cell clone formation assay and EdU assay. Transwell test was used to detect the ability of cell invasion, and apoptosis was detected by flow cytometry. WB was applied to determine the expression of apoptosis and epithelial mesenchymal transition- (EMT-) related proteins and also target proteins for observation the effect of OE-hsa_circ_0061817 on the growth of A549 cells in nude mice. Bioinformatics method was used to predict the binding microRNA (miRNA) of hsa_circ_0061817 and construct the regulatory network of competitive endogenous RNA (ceRNA) and functional analysis of miRNA target genes.

Compared with PLO-ciR group, the cell viability, proliferation, and invasive ability of A549 and LLC-LUC were significantly reduced in OE-hsa_circ_00061817 group, while the apoptosis increased in OE-hsa_circ_00061817 group compared to PLO-ciR group. WB results showed that the expression of caspase 3, caspase 7, caspase 9, and E-cadherin increased significantly, while the expression levels of vimentin and N-cadherin decreased severely. Most importantly, OE-hsa_circ_00061817 inhibited the growth of A549 tumor-bearing nude mice. According to TargetScan and mirBase databases, hsa_circ_0061817 may competitively bind hsa_mir-181b-3p, hsa-mir-337-3p, hsa-mir-421, and hsa-mir-548d-3p. The results of functional enrichment showed that miRNA target genes were involved in many cancer-related biological processes, including negative regulation of apoptosis, gene expression, transcriptional imbalance in cancer, transforming growth factor-β, and P53 signal pathway.

Over expression of hsa_circ_0061817 inhibits the proliferation of lung adenocarcinoma A549 and LLC-LUC cells and may reduce the invasive ability of lung adenocarcinoma cells by weakening the process of EMT, which provides a new target for the prevention and treatment of lung adenocarcinoma.

## Linked entities

- **Genes:** Casp3 (caspase 3) [NCBI Gene 12367], Casp7 (caspase 7) [NCBI Gene 12369], Casp9 (caspase 9) [NCBI Gene 12371], shg (shotgun) [NCBI Gene 37386], PRELID1 (PRELI domain containing 1) [NCBI Gene 737446], CadN (Cadherin-N) [NCBI Gene 35070]
- **Proteins:** Casp3 (caspase 3), Casp7 (caspase 7), Casp9 (caspase 9), shg (shotgun), PRELID1 (PRELI domain containing 1), CadN (Cadherin-N)
- **Diseases:** lung adenocarcinoma (MONDO:0005061)
- **Species:** Homo sapiens (taxon 9606), Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** CASP9 (caspase 9) [NCBI Gene 842] {aka APAF-3, APAF3, ICE-LAP6, MCH6, PPP1R56}, CASP7 (caspase 7) [NCBI Gene 840] {aka CASP-7, CMH-1, ICE-LAP3, LICE2, MCH3}, Trp53-ps (transformation related protein 53, pseudogene) [NCBI Gene 22060], VIM (vimentin) [NCBI Gene 7431], CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, MIR421 (microRNA 421) [NCBI Gene 693122] {aka MIRN421, hsa-mir-421}, CDH2 (cadherin 2) [NCBI Gene 1000] {aka ACOGS, ADHD8, ARVD14, CD325, CDHN, CDw325}
- **Diseases:** cancer (MESH:D009369), Lung Cancer (MESH:D008175), lung adenocarcinoma (MESH:D000077192)
- **Chemicals:** PLO (-)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023), LLC-LUC — Mus musculus (Mouse), Malignant tumors of the mouse pulmonary system, Cancer cell line (CVCL_5653)

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Source: https://tomesphere.com/paper/PMC11401659