Circ_0005033 is an oncogene in laryngeal squamous cell carcinoma and regulates cell progression and Cisplatin sensitivity via miR-107/IGF1R axis

Abstract

Transcriptome expression profiles of laryngeal squamous cell carcinoma (LSCC) are altered, and we aimed to investigate expression and role of hsa_circ_0005033 (circ_0005033), microRNA (miR)-107 and insulin-like growth factor 1 receptor (IGF1R) in LSCC. Real-time PCR, western blotting and immunohistochemistry detected RNA and protein expression levels. Functional assays were performed using MTT assay, EdU assay, apoptosis assay, flow cytometry, Transwell assay, and xenograft tumor model. Direct interaction was predicted by Starbase algorithm and validated by dual-luciferase reporter assay and RNA immunoprecipitation. Expression of circ_0005033 was substantially upregulated in LSCC tissues and cells, and allied with miR-107 downregulation and IGF1R upregulation. Circ_0005033 showed a closedloop structure and long half-life. Essentially, circ_0005033 and IGF1R were competing endogenous RNAs for miR-107 via target binding. Silencing circ_0005033 facilitated apoptosis rate and lowered cell viability, proliferation, migration and invasion of LSCC cells, as well as delayed xenograft tumor growth. Allied with that, cleaved-caspase 3/8/9 expression was elevated via death receptormediated and mitochondrial pathways, and expression of matrix metalloproteinase-2 (MMP2), MMP9, cyclin D1 and proliferating cell nuclear antigen was decreased. Moreover, Cisplatin-induced inhibition of cell viability was exacerbated by inhibiting circ_0005033. These functional effects of circ_0005033 depression were consistent with those of miR-107 overexpression. Furthermore, depleting miR-107 and restoring IGF1R abated the effects of circ_0005033 knockdown and miR-107 overexpression, respectively. Circ_0005033 was oncogenic in LSCC by regulating cell progression and Cisplatin sensitivity at least via miR-107/ IGF1R axis.

CircRNA hsa_circ_0069,399 as a potential clinical prognostic marker in laryngeal squamous cell carcinoma

“…Notably, certain circRNAs have been specifically associated with LSCC progression. For instance, overexpression of circZNF609 and CDR1as has been linked to tumor growth through specific miRNA interactions [ 11 , 12 ], while the downregulation of hsa_circ_0036,722 and silencing of hsa_circ_0005033 counteract tumor proliferation and enhance chemosensitivity, respectively [ 13 , 14 ]. Presently, the exploration of circRNAs in the context of LSCC is in its nascent stages.…”

MicroRNAs as the pivotal regulators of cisplatin resistance in head and neck cancers

“…IGF1R is a receptor tyrosine kinase that promotes the PI3K/AKT pathway. Circ_0005033 increased CDDP resistance in LSCC through miR-107/IGF1R axis [ 52 ]. PETN is an inhibitor of PI3K/AKT pathway.…”

MiR-107 inhibits the malignant biological behavior of esophageal squamous cell carcinoma by targeting TPM3

“…MiR-107 can combine with the 3'-untranslated region (3'-UTR) of some encoding oncogene transcripts to induce degradation, thereby weakening cancer cell activity, invasion, and drug sensitivity, etc. (22,23).…”