CircRASSF2 promotes IGF1R and osteosarcoma metastasis via sponging miR-6838-5p

Fengyan Wang; Hong Sun; Ke Li; Kun Yang; Yang Xiang; Xiaobin Tian

doi:10.21037/atm-21-6123

CircRASSF2 promotes IGF1R and osteosarcoma metastasis via sponging miR-6838-5p

Ann Transl Med. 2022 Jan;10(1):11. doi: 10.21037/atm-21-6123.

Authors

Fengyan Wang^{1

2}, Hong Sun², Ke Li³, Kun Yang², Yang Xiang², Xiaobin Tian^{1

2}

Affiliations

¹ School of Medicine, Soochow University, Suzhou, China.
² Department of Orthopedics, Affiliated Hospital of Guizhou Medical University, Guiyang, China.
³ Department of Respiratory and Critical Care Medicine, Guizhou Provincial People's Hospital, Guiyang, China.

Abstract

Background: Osteosarcoma (OS) often occurs in children and adolescents and is highly malignant. Analyzing the pathogenesis of OS has great significance for prognosis and the discovery of new treatment strategies.

Methods: The effects and mechanism of circular RNA (circRNA) on OS were analyzed, as was the correlation between circRASSF2 and insulin-like growth factor 1 receptor (IGF1R) in data from The Cancer Genome Atlas (TCGA). The expression levels of microRNA (miR)-6838-5p and circRASSF2 in OS cells and osteoblasts were detected. The dual luciferase report was used to verify the targeting relationship. OS cells overexpressing circRASSF2, miR-6838-5p and/or IGF1R were constructed. The expression level of IGF1R and the biological behavior of the cells were detected. Eighty-two pairs of OS tissue and adjacent normal tissue samples were collected, and the levels of circRASSF2, miR-6838-5p, and IGF1R mRNA were detected by reverse transcription-quantitative PCR (RT-qPCR).

Results: Compared with osteoblasts, OS cells showed lower expression of miR-6838-5p and higher expression of circRASSF2. The dual luciferase report confirmed that miR-6838-5p targeted IGF1R. Overexpression of IGF1R significantly blocked the anticancer effects of miR-6838-5p. The dual luciferase report verified that circRASSF2 targeted miR-6838-5p, and promoted the expression of IGF1R. Overexpression of circRASSF2 not only promoted the malignant biological behavior of OS cells, but also blocked the anticancer effects of miR-6838-5p. In OS tissue, circRASSF2 and IGF1R were upregulated, and the two were positively correlated. MiR-6838-5p was downregulated, which negatively correlated with both circRASSF2 and IGF1R. High levels of circRASSF2 were associated with higher stage and metastasis of OS.

Conclusions: In conclusion, the promoting effects of IGF1R on OS are targeted by miR-6838-5p. CircRASSF2 restored the expression of IGF1R by sponging miR-6838-5p, thereby promoting the progression of OS.

Keywords: Osteosarcoma (OS); circRASSF2; insulin-like growth factor 1 receptor (IGF1R); microRNA-6838-5p (miR-6838-5p).