UTMD-mediated delivery of miR-21-5p inhibitor suppresses the development of lung cancer

Xiaoyu Zhou; Haitao Liu; Yingying Pang; Muqun Wang; Shengming Liu

doi:10.1016/j.tice.2021.101719

UTMD-mediated delivery of miR-21-5p inhibitor suppresses the development of lung cancer

Tissue Cell. 2022 Feb:74:101719. doi: 10.1016/j.tice.2021.101719. Epub 2021 Dec 23.

Authors

Xiaoyu Zhou¹, Haitao Liu², Yingying Pang², Muqun Wang², Shengming Liu³

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Jinan University, 613 W. Huangpu Avenue, Guangzhou City, Guangdong Province, 510630, China; Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical College, 287 Changhuai Road, Longzihu District, Bengbu City, Anhui Province, 233000, China.
² Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical College, 287 Changhuai Road, Longzihu District, Bengbu City, Anhui Province, 233000, China.
³ Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Jinan University, 613 W. Huangpu Avenue, Guangzhou City, Guangdong Province, 510630, China. Electronic address: tlsm@jnu.edu.cn.

PMID: 34979378
DOI: 10.1016/j.tice.2021.101719

Abstract

Background: Ultrasound-targeted microbubble destruction (UTMD) is a new type of gene delivery technology. MiR-21-5p was highly expressed in a variety of cancers. In this paper, miR-21-5p inhibitor was transfected into lung cancer cells by UTMD to observe its role in lung cancer.

Methods: StarBase was used to analyze the miR-21-5p expression in lung cancer patients and its relationship with the prognosis of the patients. MiR-21-5p expression in lung cancer tissues or cell lines was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Effects of gradient concentration (0, 5, 10, 20, 30%) of SonoVue or gradient mechanical index (MI) (0, 0.5, 1, 1.5, 2 W/cm²) on the cell viability were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The targeting relationship between miR-21-5p and B-cell translocation gene 2 (BTG2) was predicted by TargetScan and confirmed by dual-luciferase reporter assay, while the expressions of the two genes were determined by qRT-PCR. Through liposome transfection or UTMD transfection, the effects of miR-21-5p/BTG2 on the biological behaviors of lung cancer cells, the size of xenograft tumors and the expressions of ki67 and miR-21-5p were measured by qRT-PCR, western blot, cell function experiments and immunohistochemistry, respectively.

Results: MiR-21-5p expression was upregulated in lung cancer, which was associated with a poor prognosis. The optimal ultrasound conditions were 10% SonoVue concentration and 1 W/cm². UTMD transfection exerted a stronger effect than liposome transfection. MiR-21-5p promoted cell viability, proliferation and migration yet suppressed apoptosis by targeting BTG2. MiR-21-5p inhibitor reduced the size and volume of xenograft tumor and the expressions of ki67 and miR-21-5p in xenograft tumor tissues.

Conclusion: UTMD-mediated miR-21-5p inhibitor can more effectively suppress the development of lung cancer.

Keywords: B-cell translocation gene 2; Lung cancer; Ultrasound-targeted microbubble destruction; miR-21-5p.

MeSH terms

A549 Cells
Humans
Lung Neoplasms* / metabolism
Lung Neoplasms* / therapy
MicroRNAs* / metabolism
MicroRNAs* / pharmacology
Microbubbles*
Ultrasonic Therapy*

Substances

MIRN21 microRNA, human
MicroRNAs