CircGDI2 Regulates the Proliferation, Migration, Invasion and Apoptosis of OSCC via miR-454-3p/FOXF2 Axis

Abstract

Background: Aberrant expression of circular RNA (circRNA) is involved in the occurrence and development of multifarious cancers, including oral squamous cell carcinoma (OSCC). However, the biological role of circGDI2 and the action mechanism in OSCC remain largely unclear. Methods: The expression levels of circGDI2, miR-454-3p and forkhead box F2 (FOXF2) were examined by quantitative real-time PCR (qRT-PCR) or Western blot. The stability of circGDI2 was confirmed by Ribonuclease R (RNase R) assay. Cell Counting Kit 8 (CCK8) assay, colony formation and transwell assay were used to detect cell proliferation, migration or invasion. Cell apoptosis was tested by flow cytometry. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were employed to verify the interaction between miR-454-3p and circGDI2 or FOXF2. Moreover, xenograft mouse models were constructed to assess tumor growth in vivo. Results: CircGDI2 was a stable circRNA and was low expressed in OSCC tissues and cells. CircGDI2 overexpression could effectively inhibit the proliferation, migration, invasion and promote apoptosis in OSCC cells, and suppress OSCC tumor growth in nude mice in vivo. MiR-454-3p could be sponged by circGDI2, and its overexpression could mitigate the suppressive effects of circGDI2 overexpression on OSCC progression. In addition, FOXF2 was a target of miR-454-3p, and miR-454-3p silence could impede the cell growth of OSCC cells by enhancing FOXF2 expression. Meanwhile, circGDI2 positively regulated FOXF2 expression by targeting miR-454-3p. Conclusion: CircGDI2 served as a repressor to restrain OSCC malignancy via miR-454-3p/ FOXF2 axis, which might be a novel biomarker for targeted OSCC therapy.

RETRACTED ARTICLE: MIR600HG sponges miR-125a-5p to regulate glycometabolism and cisplatin resistance of oral squamous cell carcinoma cells via mediating RNF44

“…Oral squamous cell carcinoma (OSCC) is a metastatic and aggressive malignant oral malignancy with an increasing incidence [ 1 ]. Currently, although progresses have been made in the administration and diagnosis of OSCC, the survival rate of OSCC patients is still disappointing due to the high recurrence rate, later diagnosis at advanced stages, and a lack of early diagnostic biomarkers [ 2 ].…”

Cytoplasmic IGF2BP2 Protein Expression in Human Patients with Oral Squamous Cell Carcinoma: Prognostic and Clinical Implications

“…OSCC has been linked to genetic modifications, including mutations to chromosomes 3, 9, 11, and 13 47 , 48 . Increasing survival rates and improving the quality of life of OSCC patients will depend on the identification of molecular biomarkers and therapeutic techniques for the diagnosis and treatment of OSCC 49 .…”

“…OSCC has been linked to genetic modifications, including mutations to chromosomes 3, 9, 11, and 13 [47,48]. Increasing survival rates and improving the quality of life of OSCC patients will depend on the identification of molecular biomarkers and therapeutic techniques for the diagnosis and treatment of OSCC [49]. Note that the specific mechanism underlying OSCC tumorigenesis has yet to be elucidated, and there are currently no reliable early indicators for the diagnosis or prognosis of OSCC [8,50].…”

Tumor Suppressor 4.1N/EPB41L1 is Epigenetic Silenced by Promoter Methylation and MiR-454-3p in NSCLC

“…In NSCLC, our study showed aberrantly high-expressed miR-454-3p directly bound to 4.1N/ EPB41L1 mRNA 3′UTR and led to the depression of tumor suppressor 4.1N/ EPB41L1 at the posttranscriptional level, uncovering the known miRNAs regulating 4.1N/ EPB41L1 . It has been reported that the miR-454-3p also acts as oncomiRNA in oral squamous cell carcinoma ( Shi et al, 2021 ), cervical cancer ( Guo et al, 2018 ; Shukla et al, 2019 ; Song et al, 2019 ; Li et al, 2021 ), liver cancer ( Li et al, 2019 ), breast cancer ( Ren et al, 2019 ; Wang et al, 2020 ), and colon cancer ( Li et al, 2018 ). Moreover, an integrative bioinformatics analysis indicates that miR-454-3p is a biomarker for diagnosing some cancers, including the LUAD ( Botling et al, 2013 ), which needs further confirmation studies in the future.…”