RETRACTED ARTICLE: The circular RNA circ-ITCH acts as a tumour suppressor in osteosarcoma via regulating miR-22

Abstract

Background: Osteosarcoma (OS) is the most prevailing primary bone tumour and the third prevalent tumour in children and adolescents. Despite advanced treatments, the survival rate of OS has not been effectively improved. Here, we intended to investigate the functional impacts of circ-ITCH on OS. Methods: Circ-ITCH expression in OS tissues and cells was evaluated utilizing qRT-PCR. Viability and proliferation of MG63 and Saos-2 cells were determined by utilizing CCK-8 assay and BrdU assay. Transwell assay was utilized to investigate migration and invasion. Western blot was utilized to distinguish apoptosis and metastasis-related proteins expression. Sequentially, the above-mentioned parameters were reassessed when up-regulating miR-22. Results: Circ-ITCH was low expressed in OS tissues and cells. Overexpressing circ-ITCH facilitated apoptosis and repressed viability, proliferation, migration and invasion in MG63 and Saos-2 cells. MiR-22 expression was reduced by overexpressing circ-ITCH. The decline of viability, proliferation, migration and invasion made by overexpressing circ-ITCH was alleviated by up-regulating miR-22. Conclusively, circ-ITCH suppressed PTEN/PI3K/AKT and SP-1 pathways via down-regulating miR-22. Conclusion: Circ-ITCH took effects on apoptosis, viability, proliferation, migration and invasion through restraining PTEN/PI3K/AKT and SP-1 pathways via down-regulating miR-22 in MG63 and Saos-2 cells. HIGHLIGHTS 1. Low expression of circ-ITCH is observed in osteosarcoma tissues and cell lines; 2. Overexpression circ-ITCH suppresses miR-22 expression; 3. Circ-ITCH promotes proliferation and represses apoptosis by up-regulating miR-22; 4. Circ-ITCH promotes migration and invasion by up-regulating miR-22; 5. Circ-ITCH activates PTEN/PI3K/AKT and SP-1 pathways by up-regulating miR-22.

The interplay between m6A RNA methylation and noncoding RNA in cancer

“…Studies have confirmed that circRNAs, as miRNA sponges, competitively bind miRNAs and affect their activity and the expression of their downstream target genes [90,[108][109][110]. MiRNA regulation by circRNAs has been identified in some cancers [111][112][113][114][115]. Moreover, miRNAs have been shown to regulate m6A modifications [40,41].…”

Emerging Roles and Potential Biological Value of CircRNA in Osteosarcoma

“…However, another study carried out by Ren et al (74) stated the opposite result-that circ-ITCH had lower expression in OSA cells and was identified in clinical human OSA and para-tumor tissues. Their data showed that overexpression of circ-ITCH led to reduced SP-1 expression via PTEN/phosphoinositide 3-kinase (PI3K)/AKT pathways, which in turn suppressed proliferation, migration, and invasion by downregulating miR-22 (74). This is in concert with the conclusion that circ-ITCH might serve as an anti-oncogene via sponging multiple oncogenic miRNAs in multiple tumors, including ovarian cancer, prostate cancer, melanoma, gastric cancer, glioma, breast cancer, bladder cancer, papillary thyroid cancer, lung cancer, hepatocellular carcinoma, esophageal squamous cell carcinoma, and colorectal cancer (91,92).…”

“…Further mechanistic studies revealed that circ-ITCH could promote the growth, migration, and invasion of OSA cells and even enhance epidermal growth factor receptor expression by reducing levels of miR-7 (30). However, another study carried out by Ren et al (74) stated the opposite result-that circ-ITCH had lower expression in OSA cells and was identified in clinical human OSA and para-tumor tissues. Their data showed that overexpression of circ-ITCH led to reduced SP-1 expression via PTEN/phosphoinositide 3-kinase (PI3K)/AKT pathways, which in turn suppressed proliferation, migration, and invasion by downregulating miR-22 (74).…”

PTEN, a Barrier for Proliferation and Metastasis of Gastric Cancer Cells: From Molecular Pathways to Targeting and Regulation

“…However, further research demonstrated that circRNAs are a distinct type of RNA molecule with modulatory effects on cellular events [ 143 , 144 , 145 , 146 ]. In the case of PTEN signaling, different experiments have shown that circRNAs are able to act as upstream mediators of the PTEN signaling pathway in cancer cells [ 147 , 148 , 149 ]. This section is devoted to investigating the role of circRNAs in the regulation of PTEN in GC cells.…”