Cancer Management and Research (Oct 2020)
Knockdown of CircCRIM1 Inhibits HDAC4 to Impede Osteosarcoma Proliferation, Migration, and Invasion and Facilitate Autophagy by Targeting miR-432-5p
Abstract
Jun Liu,1 Guang Feng,2 Zhengwei Li,3 Rui Li,1 Peng Xia1 1Department of Hand Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130000, People’s Republic of China; 2The Fourth Medical Center of PLA General Hospital, Beijing 100048, People’s Republic of China; 3Department of Orthopaedics, The Second Hospital of Jilin University, Jilin 130000, People’s Republic of ChinaCorrespondence: Peng XiaDepartment of Orthopaedics, The Second Hospital of Jilin University, No. 218 Ziqiang Street, Nanguan District, Changchun 130000, Jilin Province, People’s Republic of China, Tel +86-043181136193Email [email protected]: 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.Keywords: circCRIM1, osteosarcoma, miR-432-5p, HDAC4
