Knockdown of CircCRIM1 Inhibits HDAC4 to Impede Osteosarcoma Proliferation, Migration, and Invasion and Facilitate Autophagy by Targeting MiR-432-5p

Overview

Journal Cancer Manag Res

Publisher Dove Medical Press

Specialty Oncology

Date 2020 Oct 29

PMID 33116874

Citations 11

Authors

Jun Liu

Guang Feng

Zhengwei Li

Rui Li

Peng Xia

Affiliations

Soon will be listed here.

Abstract

Background: Circular RNAs (circRNAs) serve for a genre of considerable modulatory molecules that have been largely researched in human cancers. However, the contribution of circRNA cysteine-rich transmembrane bone morphogenetic protein regulator 1 (circCRIM1) to osteosarcoma (OS) is completely unclear.

Methods: All the RNA levels were examined via quantitative real-time polymerase chain reaction (qRT-PCR). Cellular proliferation and migration/invasion were, respectively, analyzed using 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay and transwell assay. The determination of all protein expression was administrated by Western blot. Dual-luciferase reporter assay was used for proving the target combination. The exploration of circCRIM1 in vivo was performed by xenograft assay.

Results: In OS tissues and cells, circCRIM1 was differentially up-regulated. Functionally, cell proliferation, migration and invasion were suppressed while autophagy was promoted after circCRIM1 was down-regulated in OS cells. Mechanistically, mircoRNA-432-5p (miR-432-5p) was a miRNA target of circCRIM1 and the inhibitory effect of circCRIM1 knockdown on OS progression was achieved by targeting miR-432-5p. Moreover, histone deacetylase 4 (HDAC4) was a downstream gene of miR-432-5p and circCRIM1 targeted miR-432-5p to up-regulate HDAC4 level. MiR-432-5p inhibited proliferation, migration, and invasion but enhanced autophagy of OS cells through down-regulating HDAC4. In vivo, knockdown of circCRIM1 decreased OS growth via acting on the miR-432-5p/HDAC4 axis.

Conclusion: Our findings elucidated the oncogenic function of circCRIM1 in OS via the regulation of the miR-432-5p/HDAC4 axis, affording a novel view about how circRNA participated in OS development.

Citing Articles

Trends and future directions of autophagy in osteosarcoma: A bibliometric analysis.

Shang J, Zhao F, Xie L, Wang Y, Li B, Jin C Open Med (Wars). 2024; 19(1):20241080.

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Alteration in the Expression of Circular Rnas and its association with the Development and Progression of Osteosarcoma, an Integrative Review with High Sensitivity Research.

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Tang S, Cai L, Wang Z, Pan D, Wang Q, Shen Y Cancer Innov. 2023; 2(6):463-487.

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Chen J, Hei R, Chen C, Wu X, Han T, Bian H Am J Cancer Res. 2023; 13(8):3463-3481.

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