Abnormal DRP1 expression has been identified in a variety of human cancers. However, the prognostic potential and mechanistic role of DRP1 in head and neck cancer (HNC) are currently poorly understood. Here, we demonstrated a significant upregulation of DRP1 in HNC tissues, and that DRP1 expression correlates with poor survival of HNC patients. Diminished DRP1 expression suppressed tumor growth and metastasis in both in vitro and in vivo models. DRP1 expression was positively correlated with FOXM1 and MMP12 expression in HNC patient samples, suggesting pathological relevance in the context of HNC development. Moreover, DRP1 depletion affected aerobic glycolysis through the downregulation of glycolytic genes, and overexpression of MMP12 in DRP1-depleted cells could help restore glucose consumption and lactate production. Using ChIP-qPCR, we showed that DRP1 modulates FOXM1 expression, which can enhance MMP12 transcription by binding to its promoter. We also showed that miR-575 could target 3'UTR of DRP1 mRNA and suppress DRP1 expression. Collectively, our study provides mechanistic insights into the role of DRP1 in HNC and highlights the potential of targeting the miR-575/DRP1/FOXM1/MMP12 axis as a novel therapy for the prevention of HNC progression.

The role of miRNAs in cancer and their possible function as therapeutic agents are interesting and needed further investigation. The miR-26a-5p had been demonstrated as a tumor suppressor in various cancers. However, the importance of miR-26a-5p regulation in upper tract urothelial carcinoma (UTUC) remains unclear. Here, we aimed to explore the miR-26a-5p expression in UTUC tissues and to identify its regulatory targets and signal network involved in UTUC tumorigenesis. The miR-26a-5p expression was validated by quantitative real-time polymerase chain reaction (qPCR) using renal pelvis tissue samples from 22 patients who were diagnosed with UTUC and 64 cases of renal pelvis tissue microarray using in situ hybridization staining. BFTC-909 UTUC cells were used to examine the effects of miR-26a-5p genetic delivery on proliferation, migration and expression of epithelial-to-mesenchymal transition (EMT) markers. MiR-26a-5p was significantly down-regulated in UTUC tumors compared to adjacent normal tissue and was decreased with histological grades. Moreover, restoration of miR-26a-5p showed inhibition effects on proliferation and migration of BFTC-909 cells. In addition, miR-26a-5p delivery regulated the EMT marker expression and inhibited WNT5A/β-catenin signaling and expression of downstream molecules including NF-κB and MMP-9 in BFTC-909 cells. This study demonstrated that miR-26a-5p restoration may reverse EMT process and regulate WNT5A/β-catenin signaling in UTUC cells. Further studies warranted to explore the potential roles in biomarkers for diagnostics and prognosis, as well as novel therapeutics targets for UTUC treatment.

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Background: For lymphedema patients who received a vascularized lymph node flap transfer (VLNT) as their primary treatment, what are the treatment options when they seek further improvement? With recent publications supporting the use of lymphaticovenous anastomosis (LVA) for treating severe lymphedema, we examined whether LVA could benefit post-VLNT patients seeking further improvement. Methods: This retrospective cohort study enrolled eight lymphedema patients with nine lymphedematous limbs (one patient suffered from bilateral lower limb lymphedema) who had received VLNT as their primary surgery. Patients with previous LVA, liposuction, excisional therapy, or incomplete data were excluded. LVA was performed on nine lower lymphedematous limbs. Demographic data and intraoperative findings were recorded. Preoperative and postoperative limb volumes were measured with magnetic resonance volumetry. The primary outcome was the limb volume measured 6 months post-LVA. Results: The median duration of lymphedema before LVA was 10.5 (4.9–15.3) years. The median waiting time between VLNT and LVA was 41.4 (22.3–97.9) months. The median volume gained in the lymphedematous limb was 3836 (2505–4584) milliliters (mL). The median post-LVA follow-up period was 18 (6–30) months. Significant 6-month and 1-year post-LVA percentage volume reductions were found compared to pre-LVA volume (both p < 0.001). Conclusion: Based on the results from this study, the authors recommend the use of LVA as a secondary procedure for post-VLNT patients seeking further improvement.