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Circ-LDLRAD3 Enhances Cell Growth, Migration, and Invasion and Inhibits Apoptosis by Regulating MiR-224-5p/NRP2 Axis in Gastric Cancer

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Abstract

Background

Emerging as a newly discovered type of noncoding RNAs, circular RNAs have been manifested as a crucial regulator in tumorigenesis of human malignancies, including gastric cancer (GC). Although circ-LDLRAD3 has been revealed as an oncogene in pancreatic cancer, the underlying role of circ-LDLRAD3 in GC remains poorly understood.

Aims

Exploring the underlying function of circ-LDLRAD3 on GC progression.

Methods

Circ-LDLRAD3 expression was detected through RT-qPCR. EdU, colony formation, TUNEL, and transwell assays were performed to analyze the function of circ-LDLRAD3 on GC progression. Luciferase reporter and RIP assays were applied to testify the interaction between circ-LDLRAD, miR-224-5p, and NRP2 in GC.

Results

We detected preliminarily the expression of circ-LDLRAD3 and observed a markedly high expression of circ-LDLRAD3 in GC cells. Besides, circ-LDLRAD3 was featured with loop structure. Biological function assays testified that silenced circ-LDLRAD3 inhibited cell proliferation, migration, and invasion capacity but facilitated apoptosis of GC cells. Molecular mechanism assays uncovered that circ-LDLRAD3 combined with miR-224-5p in GC. Moreover, rescue assays delineated that inhibited expression of miR-224-5p could restore the inhibitive influence of circ-LDLRAD3 knockdown on the progression of GC. Moreover, neuropilin 2 (NRP2) was a downstream target of miR-224-5p. Additionally, circ-LDLRAD3 regulated NRP2 expression by sponging miR-224-5p in GC. Furthermore, circ-LDLRAD3 depletion-mediated effect on GC progression could be reversed by overexpressing NRP2.

Conclusions

Circ-LDLRAD3 facilitates GC progression by regulating miR-224-5p/NRP2 axis, providing new insights for the researches of GC treatment.

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Acknowledgment

The authors manifest great appreciation to all those involved in this research.

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Authors and Affiliations

  1. The Department of Geriatric Oncology, The Fourth People’s Hospital of Shenyang, Shenyang, 110031, Liaoning, China

    Yan Wang & Xin Chen

  2. Department of Medical Oncology, People’s Hospital of Lianshui County, No. 6 East Hongri Avenue, Lianshui County, Huaian, 223400, Jangsu, China

    Hailin Yin

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  1. Yan Wang
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Correspondence to Hailin Yin.

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Wang, Y., Yin, H. & Chen, X. Circ-LDLRAD3 Enhances Cell Growth, Migration, and Invasion and Inhibits Apoptosis by Regulating MiR-224-5p/NRP2 Axis in Gastric Cancer. Dig Dis Sci 66, 3862–3871 (2021). https://doi.org/10.1007/s10620-020-06733-1

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