MIR-222 REGULATES THE PROGRESSION OF ORAL SQUAMOUS CELL CARCINOMA BY TARGETING CDKN1B

Introduction: Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive form of cancer affecting the oral cavity, with significant morbidity and mortality. Recent studies have highlighted the role of microRNAs (miRNAs) in cancer progression, including their potential as therapeutic targets. This study investigates the role of microRNA-222 (miR-222) in the progression of OSCC by targeting CDKN1B, a critical regulator of cell cycle and apoptosis. Understanding this relationship could provide insights into novel therapeutic strategies for OSCC.

Key Findings: The study revealed that miR-222 levels were significantly elevated in OSCC tissues and cells compared to adjacent normal tissues and cells. Overexpression of miR-222 in OSCC cells increased cell proliferation, migration, and cell cycle progression while inhibiting apoptosis. Conversely, upregulation of CDKN1B expression inhibited cell viability, migration, and invasiveness and promoted apoptosis. The dual-luciferase reporter gene assay confirmed that miR-222 directly targets CDKN1B, inhibiting its expression. In vivo assays demonstrated that miR-222 promotes tumor growth by targeting CDKN1B, as evidenced by increased tumor weight and volume in cell-derived xenograft models.

Innovative Tools: The researchers employed various creative methods to analyze the effects of miR-222 on OSCC progression. Cell viability was assessed using the MTT assay, while cell metastasis and apoptosis were measured using transwell assays and flow cytometry, respectively. The targeting relationship between miR-222 and CDKN1B was verified using dual-luciferase reporter gene assays and Western blot analysis. In vivo, the effects miR-222 were evaluated using cell-derived xenograft models, with tumor growth assessed by measuring tumor weight and volume. Additionally, hematoxylin-eosin and immunohistochemical staining were used to determine tumor tissue proliferation.

Behavioral Assessments: Overexpression of miR-222 in OSCC cells significantly increased cell proliferation and migration while reducing apoptosis. The miR-222 mimic group showed enhanced tumor cell proliferation, migration, and cell cycle progression, with a marked decrease in apoptosis. These effects were confirmed in vivo, where miR-222 overexpression led to increased tumor growth, as indicated by greater tumor weight and volume in xenograft models.

Biochemical Analysis: The study identified CDKN1B as a direct target of miR-222. Overexpression of CDKN1B inhibited cell viability, migration, and invasiveness while promoting apoptosis in OSCC cells. The dual-luciferase reporter gene assay showed that miR-222 binds directly to the 3' untranslated region of CDKN1B, inhibiting its expression. Western blot analysis confirmed that miR-222 downregulated CDKN1B protein levels. In vivo, miR-222 overexpression in xenograft models reduced CDKN1B expression, correlating with increased tumor growth.

Conclusions: This study demonstrates that miR-222 plays a significant role in the progression of OSCC by targeting and downregulating CDKN1B. The upregulation of miR-222 in OSCC tissues and cells promotes tumor growth, cell proliferation, and migration while inhibiting apoptosis. Targeting miR-222 could potentially serve as a therapeutic strategy for OSCC by restoring CDKN1B expression and inhibiting tumor progression. Future research should explore the clinical applications of miR-222 inhibitors in OSCC treatment and further elucidate the molecular mechanisms underlying miR-222 and CDKN1B interactions.

Join the Discussion: We invite you to share your thoughts on the implications of these findings for understanding the molecular mechanisms underlying OSCC progression. How might targeting miR-222 influence the development of therapeutic strategies for OSCC? What other molecular pathways could be involved in regulating CDKN1B in cancer? Join the conversation in the comments below and share your insights and ideas.

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Original Research: The original research, "MiR-222 regulates the progression of oral squamous cell carcinoma by targeting CDKN1B," is available on PubMed here.