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CircARL8B Contributes to the Development of Breast Cancer Via Regulating miR-653-5p/HMGA2 Axis

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Abstract

Circular RNAs (circRNAs) act as essential regulators in breast cancer (BC) progression. In this paper, we aimed to investigate the functions of circARL8B in BC. The levels of circARL8B, ADP Ribosylation Factor Like GTPase 8B (ARL8B), miR-653-5p and high-mobility group AT-hook 2 (HMGA2) mRNA were examined by qRT-PCR. The stability of circARL8B was determined by RNase R assay and Actinomycin D assay. Cell viability and metastasis were evaluated by Cell Counting Kit-8 (CCK-8) assay and transwell assay, respectively. The levels of cellular phospholipids and triglycerides were measured using relevant kits. Protein levels were measured by western blot analysis. The association between miR-653-5p and circARL8B or HMGA2 was verified by dual-luciferase reporter assay. A murine xenograft model was established to explore the function of circARL8B in vivo. CircARL8B was increased in BC tissues and cells. CircARL8B silencing inhibited cell viability, migration, invasion and fatty acid metabolism in BC cells in vitro and blocked tumor growth in vivo. MiR-653-5p was identified as the target of circARL8B and miR-653-5p was negatively modulated by circARL8B. The suppressive role of circARL8B silencing in BC cell progression was abolished by miR-653-5p downregulation. Moreover, HMGA2 was the target gene of miR-653-5p. HMGA2 overexpression abrogated the effect of miR-653-5p on BC cell development. In addition, circARL8B knockdown might block PGE2/PI3K/AKT/GSK-3β/Wnt/β-catenin pathway. Silencing of circARL8B inhibited cell viability, migration, invasion and fatty acid metabolism via miR-653-5p/HMGA2 axis in BC.

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Data Availability

All data generated or analyzed during this study are included in this article.

Abbreviations

BC:

Breast cancer

CircRNA:

Circular RNA

MiRNA:

MicroRNA

HMGA2:

High-mobility group AT-hook 2

ARL8B:

ADP Ribosylation Factor Like GTPase 8B

ncRNAs:

Non-coding RNAs

COL1A1:

Collagen type I alpha 1 chain

ACACA:

Acetyl-CoA carboxylase alpha

FASN:

Fatty acid synthase

ZEB2:

Zinc finger E-box binding homeobox 2

RPMI1640:

Roswell Park Memorial Institute 1640 Medium

FBS:

Fetal bovine serum

qRT-PCR:

Quantitative real-time polymerase chain reaction

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

CCK-8:

Cell Counting Kit-8

RIPA:

Radio Immunoprecipitation Assay

SDS-PAGE:

Sodium dodecyl sulfonate-polyacrylamide gel

PVDF:

Polyvinylidene difluoride membranes

ACC1:

Acetyl-CoA carboxylase 1

FABP5:

Fatty acid binding protein-5

PGE2:

Prostaglandin E2

ECL:

Enhanced chemiluminescence

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Funding

This study supported by 2018 Guangdong Province Science and Technology Innovation Strategy Special Fund (Vertical Collaborative Management Direction) Project, Shan Fuke [2018] 157.

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Author notes

  1. Hansheng Wu, Jingyun Xu have contributed equally to this work.

Authors and Affiliations

  1. Department of Thoracic Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China

    Hansheng Wu

  2. Department of Pathology, The First Affiliated Hospital of Shantou University Medical College, No. 57, Changping Road, Shantou, 515041, Guangdong, China

    Jingyun Xu & Guoliang Gong

  3. Department of Pathology, Chaonan Minsheng Hospital of Shantou, Shantou, Guangdong, China

    Guoliang Gong, Yuanxin Zhang & Shenggui Wu

Authors
  1. Hansheng Wu
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  2. Jingyun Xu
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  3. Guoliang Gong
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  4. Yuanxin Zhang
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  5. Shenggui Wu
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Correspondence to Guoliang Gong.

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Wu, H., Xu, J., Gong, G. et al. CircARL8B Contributes to the Development of Breast Cancer Via Regulating miR-653-5p/HMGA2 Axis. Biochem Genet 59, 1648–1665 (2021). https://doi.org/10.1007/s10528-021-10082-7

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