# Circ_0028826 Promotes Growth and Metastasis of NSCLC via Acting as a Sponge of miR‐758‐3p to Derepress IDH2 Expression

**Authors:** Lihong Guo, Xueqin Liu, Jie Zhang, Zhuixing Liu, Bohao Zhang, Yang Sun, Dandan Cui, Jinpeng Liu

PMC · DOI: 10.1111/crj.13802 · The Clinical Respiratory Journal · 2024-08-07

## TL;DR

This study shows that a circular RNA called circ_0028826 helps lung cancer grow and spread by blocking a microRNA that normally limits another gene, IDH2.

## Contribution

The paper identifies a novel regulatory mechanism involving circ_0028826, miR-758-3p, and IDH2 in non–small cell lung cancer.

## Key findings

- Circ_0028826 is overexpressed in NSCLC and promotes cancer cell growth and metastasis.
- Circ_0028826 acts as a sponge for miR-758-3p, leading to increased IDH2 expression.
- Knockdown of circ_0028826 inhibits tumor growth in a xenograft model.

## Abstract

Non–small cell lung cancer (NSCLC) is one of the cancers with the highest mortality and morbidity in the world. Circular RNAs (circRNAs) are newly identified players in carcinogenesis and development of various cancers. This study is aimed at exploring the functional effects and mechanism of circ_0028826 in the development of NSCLC.

Real‐time quantitative PCR (RT‐qPCR) was used to detect the expression levels of circ_0028826, IDH2 mRNA, and miR‐758‐3p. IDH2, Bcl2, Bax, and E‐cadherin protein levels were detected using a western blot. Cell Counting Kit‐8 (CCK‐8), 5‐ethynyl‐2′‐deoxyuridine (EdU), flow cytometry, wound healing, and transwell assays were used to assess the capacities of proliferation, apoptosis, migration, and invasion. Interaction between miR‐758‐3p and circ_0028826 or IDH2 was validated using a dual‐luciferase reporter assay. The role of circ_0028826 in vivo was checked based on a xenograft tumor model.

Circ_0028826 was elevated in NSCLC, and its absence inhibited NSCLC cell proliferation, migration, invasion, and induced apoptosis. In terms of mechanism, circ_0028826 increased IDH2 expression by targeting miR‐758‐3p. In addition, circ_0028826 knockdown also regulated IDH2 by targeting miR‐758‐3p to inhibit tumor growth in vivo.

Circ_0028826 promoted the development of NSCLC via regulation of the miR‐758‐3p/IDH2 axis, providing a new strategy for NSCLC treatment.

Circ_0028826 expression was upregulated in NSCLC patients and cell lines, and its knockdown might inhibit proliferation, migration, and invasion and induce apoptosis in NSCLC cells via targeting the miR‐758‐3p/IDH2 axis.

## Linked entities

- **Genes:** IDH2 (isocitrate dehydrogenase (NADP(+)) 2) [NCBI Gene 3418]
- **Proteins:** IDH2 (isocitrate dehydrogenase (NADP(+)) 2), BCL2 (BCL2 apoptosis regulator), BAX (BCL2 associated X, apoptosis regulator), shg (shotgun)
- **Diseases:** non–small cell lung cancer (MONDO:0005233), NSCLC (MONDO:0005233)

## Full-text entities

- **Genes:** IDH2 (isocitrate dehydrogenase (NADP(+)) 2) [NCBI Gene 3418] {aka D2HGA2, ICD-M, IDH, IDH-2, IDHM, IDP}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}
- **Diseases:** Metastasis (MESH:D009362), cancers (MESH:D009369), NSCLC (MESH:D002289)
- **Chemicals:** 5-ethynyl-2'-deoxyuridine (MESH:C031086)
- **Cell lines:** Circ_0028826 — Homo sapiens (Human), Alport syndrome, Induced pluripotent stem cell (CVCL_LF09)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11306285/full.md

## References

28 references — full list in the complete paper: https://tomesphere.com/paper/PMC11306285/full.md

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Source: https://tomesphere.com/paper/PMC11306285