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Circular hsa_circ_0020377 regulates KLF7 by targeting miR-194-5p to facilitate tumor cell malignant behaviors and glycolysis in oral squamous cell carcinoma progression

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Abstract

Oral squamous cell carcinoma (OSCC) is a common malignant tumor with high recurrence, metastasis rates, and poor prognosis. Numerous studies discover that circular RNA (circRNA) is closely associated with OSCC progression. Hsa_circ_0020377 has been aberrantly expressed in OSCC, but its role in tumor growth and metastasis remains largely unclear. Hsa_circ_0020377, microRNA-194-5p (miR-194-5p), and Krüppel-like factor 7 (KLF7) contents were determined by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferative, cycle progression migration, and invasion were measured using 5-ethynyl-2′-deoxyuridine (EdU), Cell Counting Kit-8 (CCK-8), flow cytometry, wound healing, and Transwell assays. The glycolysis level was detected via specific kits. Cyclin D1, E-cadherin, hexokinase 2 (HK2), and KLF7 protein levels were detected via western blot. Using predicting bioinformatics software, the binding between miR-194-5p and hsa_circ_0020377 or KLF7 was verified using a dual-luciferase reporter and RNA Immunoprecipitation (RIP). Beyond that, a xenograft tumor model was used to analyze the role of hsa_circ_0020377 on tumor cell growth in vivo. Increased hsa_circ_0020377 and KLF7 and reduced miR-194-5p were found in OSCC tissues and cell lines. Loss-of-function experiments proved that hsa_circ_0020377 depletion might block OSCC cell proliferation, cycle progression, migration, invasion, and glycolysis in vitro. In xenograft mouse models, hsa_circ_0020377 silencing might suppress tumor growth. In addition, mechanism research suggested that hsa_circ_0020377 could bind with miR-194-5p and enhance its target gene (KLF7), thereby affecting OSCC development. These results broaden our insights regarding the regulation of OSCC progression via circRNA and act as a reference for future clinical studies in OSCC diagnosis and treatment.

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Funding

This study was supported by the Hebei Provincial Health Department Key Science and Technology Research Plan (No. 20201111) and the Youth Science and technology Project of Hebei Provincial Department of Health (No. 20190694).

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Authors and Affiliations

  1. Department of Stomatology, The Fourth Hospital of Hebei Medical University, No. 12, JianKang Road, Shijiazhuang, Hebei Province, 050011, People’s Republic of China

    NaiHeng Hei, Linyu Jin, Shixiong Peng & Yang Bao

  2. Department of Stomatology, Hengshui People’s Hospital, Hengshui, Hebei Province, China

    Peng Liu

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Peng Liu designed and performed the research; Linyu Jin, Shixiong Peng, and Yang Bao analyzed the data; NaiHeng Hei wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yang Bao.

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Fig. S1

Transfection efficiency of hsa_circ_0020377, miR-194-5p, and KLF7 in OSCC cell lines. (A) RT-qPCR analysis of hsa_circ_0020377 expression in SCC-9 and HSC-3 cells transfected with sh-NC or sh-hsa_circ_0020377. (B) miR-194-5p content was detected in SCC-9 and HSC-3 cells transfected with miR-NC or miR-194-5p using RT-qPCR. (C) Western blot analysis of KLF7 protein level in SCC-9 and HSC-3 cells transfected vector or KLF7. *P <0.05. (PNG 151 kb)

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Hei, N., Liu, P., Jin, L. et al. Circular hsa_circ_0020377 regulates KLF7 by targeting miR-194-5p to facilitate tumor cell malignant behaviors and glycolysis in oral squamous cell carcinoma progression. Funct Integr Genomics 23, 52 (2023). https://doi.org/10.1007/s10142-023-00973-w

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