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The Sponge Interaction Between Circular RNA and microRNA Serves as a Fast-Evolving Mechanism That Suppresses Non-small Cell Lung Cancer (NSCLC) in Humans

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Abstract

Non-small cell lung cancer (NSCLC) is one of the most lethal cancer types in the world. Currently, the molecular mechanisms and pathways underlying NSCLC oncogenesis are poorly understood. Using multiple Omics data, we systematically explored the differentially expressed circular RNAs (circRNAs) in NSCLC. We also investigated potential microRNA sponges (that absorb circRNAs) in NSCLC and downstream target genes with experimental verifications. hsa_circ_0003497 was down-regulated in NSCLC and played an inhibitory role in tumorigenesis. In contrast, miR-197-3p was up-regulated in NSCLC. hsa_circ_0003497 directly interacts with miR-197-3p and releases a target gene of miR-197-3p termed CTNND1 (a known tumor suppressor gene). Evolutionary analysis reveals fast evolution of this hsa_circ_0003497-miR-197-3p-CTNND1-NSCLC axis in mammals. This work clarified the biological functions and molecular mechanisms of how hsa_circ_0003497 suppresses NSCLC through miR-197-3p and CTNND1. We discovered molecular markers for the prognosis of NSCLC and provided potential intervention targets for its treatment.

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Data Availability

This study did not produce raw sequence or structure data. The microarray circRNA data of three pairs of NSCLC and normal tissues were downloaded from GEO database (http://www.ncbi.nlm.nih.gov/geo) with accession number GSE112214.

Abbreviations

circRNA:

Circular RNA

ncRNA:

Non-coding RNA

miRNA:

MicroRNA

NSCLC:

Non-small cell lung cancer

LCLC:

Large cell lung cancer

LUSC:

Lung Squamous Carcinoma

LUAD:

Lung Adenocarcinoma

WT:

Wild type

NC:

Negative control

PCR:

Polymerase chain reaction

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Acknowledgements

We thank our colleagues and any people in our institution who have given precious suggestions to this work.

Funding

The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Respiratory Medicine, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, China

    Liqun Wu, Meiling Cao, Xiaoxin Pu, Baoyi Liu & Jinxiang Wang

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  1. Liqun Wu
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  2. Meiling Cao
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  3. Xiaoxin Pu
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  4. Baoyi Liu
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  5. Jinxiang Wang
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Contributions

LW, MC, XP, BL: methodology, writing—original draft. JW: conceptualization, supervision, writing—original draft and writing—review and editing.

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Correspondence to Jinxiang Wang.

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Wu, L., Cao, M., Pu, X. et al. The Sponge Interaction Between Circular RNA and microRNA Serves as a Fast-Evolving Mechanism That Suppresses Non-small Cell Lung Cancer (NSCLC) in Humans. J Mol Evol 90, 362–374 (2022). https://doi.org/10.1007/s00239-022-10067-z

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