circFNDC3B Accelerates Vasculature Formation and Metastasis in Oral Squamous Cell Carcinoma

Abstract

Emerging evidence has demonstrated that circular RNAs (circRNAs) are involved in cancer metastasis. Further elucidation of the role of circRNAs in oral squamous cell carcinoma (OSCC) could provide insights into mechanisms driving metastasis and potential therapeutic targets. Here, we identify a circRNA, circFNDC3B, that is significantly upregulated in OSCC and is positively associated with lymph node (LN) metastasis. In vitro and in vivo functional assays showed that circFNDC3B accelerated the migration and invasion of OSCC cells and the tube-forming capacity of human umbilical vein endothelial cells (HUVEC) and human lymphatic endothelial cells (HLEC). Mechanistically, circFNDC3B regulated ubiquitylation of the RNA-binding protein FUS and the deubiquitylation of HIF1A through the E3 ligase MDM2 to promote VEGFA transcription, thereby enhancing angiogenesis. Meanwhile, circFNDC3B sequestered miR-181c-5p to upregulate SERPINE1 and PROX1, which drove epithelial-mesenchymal transition (EMT) or partial-EMT (p-EMT) in OSCC cells and promoted lymphangiogenesis to accelerate lymph node metastasis. Overall, these findings uncovered the mechanistic role of circFNDC3B in orchestrating cancer cell metastatic properties and vasculature formation, suggesting circFNDC3B could be a potential target to reduce OSCC metastasis.

Development of a novel senescence‐related gene signature to predict clinical outcomes, immune landscape, and chemotherapeutic sensitivity in oral squamous cell carcinoma

“…These genes have been documented as vital agents driving tumorigenesis and promising factors with diagnostic and prognostic value throughout various human cancers including OSCC. [36][37][38][39] For example, overexpressed G6PD, PTTG1, and VEGFA in OSCC significantly associated with worse outcomes. 36,37,39 Particularly, CDK1 was frequently highly expressed across multiple cancers and promoted cancer cell proliferation and progression by facilitating cell cycle transition, cell migration, and EMT.…”

“…In this study, our in‐silicon analyses identified 7 SRGs including CDK1, G6PD, IL1A, MAD2L1, PDCD10, PTTG1, and VEGFA which were highly expressed in primary OSCC samples and associated with patient's prognosis. These genes have been documented as vital agents driving tumorigenesis and promising factors with diagnostic and prognostic value throughout various human cancers including OSCC 36–39 . For example, overexpressed G6PD, PTTG1, and VEGFA in OSCC significantly associated with worse outcomes 36,37,39 .…”

“…[36][37][38][39] For example, overexpressed G6PD, PTTG1, and VEGFA in OSCC significantly associated with worse outcomes. 36,37,39 Particularly, CDK1 was frequently highly expressed across multiple cancers and promoted cancer cell proliferation and progression by facilitating cell cycle transition, cell migration, and EMT. 40 It was also identified as an immunological and prognostic biomarker in multiple cancers.…”

N‐acetyltransferase 10 promotes the progression of oral squamous cell carcinoma through N4‐acetylcytidine RNA acetylation of MMP1 mRNA

“…The treatment of OSCC includes surgery, chemotherapy, and radiotherapy, but most patients have poor prognoses 15 . The pathogenesis of OSCC is not clear 16 . It is the focus of OSCC research to clarify its pathogenesis and development mechanism at the molecular level.…”

Evodiamine inhibits EPRS expression to regulate glutamate metabolism and proliferation of oral squamous cell carcinoma cells

“…The global toll of 170,000 deaths and over 370,000 new cases reported in the latest Global Cancer Statistics underlines its severity 1 . Despite some strides in cancer treatment research, the prognosis for OSCC patients remains grim, with a 5‐year survival rate below 50% 2 . Urgent exploration of novel therapeutic strategies is imperative.…”