MicroRNA-196a-5p is a potential prognostic marker of delayed lymph node metastasis in early-stage tongue squamous cell carcinoma

MicroRNAs (miRs) are expected to serve as prognostic tools for cancer. However, many miRs have been reported as prognostic markers of recurrence or metastasis in oral squamous cell carcinoma patients. We aimed to determine the prognostic markers in early‑stage tongue squamous cell carcinoma (TSCC). Based on previous studies, we hypothesized that miR‑10a, 10b, 196a‑5p, 196a‑3p, and 196b were prognostic markers and we retrospectively performed miR expression analyses using formalin‑fixed paraffin‑embedded sections of surgical specimens. Total RNA was isolated from cancer tissues and adjacent normal tissue as control, and samples were collected by laser‑capture microdissection. After cDNA synthesis, reverse transcription‑quantitative polymerase chain reaction was performed. Statistical analyses for patient clinicopathological characteristics, recurrence/metastasis, and survival rates were performed to discern their relationships with miR expression levels, and the 2‑ΔΔCq method was used. miR‑196a‑5p levels were significantly upregulated in early‑stage TSCC, particularly in the lymph node metastasis (LNM) group. The LNM‑free survival rate in the low miR‑196a‑5p ΔΔCq value regulation group was found to be lower than that in the high ΔΔCq value regulation group (P=0.0079). Receiver operating characteristic analysis of ΔΔCq values revealed that miR‑196a‑5p had a P‑value=0.0025, area under the curve=0.740, and a cut‑off value=‑0.875 for distinguishing LNM. To our knowledge, this is the first study to examine LNM‑related miRs in early‑stage TSCC as well as miRs and ‘delayed LNM’ in head and neck cancer. miR‑196a‑5p upregulation may predict delayed LNM. Our data serve as a foundation for future studies to evaluate miR levels and facilitate the prediction of delayed LNM during early‑stage TSCC, which prevent metastasis when combined with close follow‑up and aggressive adjuvant therapy or elective neck dissection. Moreover, our data will serve as a foundation for future studies to evaluate whether miR‑196a‑5p can serve as a therapeutic marker for preventing metastasis

Low-Dose UVB Contributes to Host Resistance against Leishmania amazonensis Infection in Mice through Induction of Gamma Interferon and Tumor Necrosis Factor Alpha Cytokines

UV radiation suppresses the immune response, a fact which raises the question of whether the phenomenon may find practical applications in the outcome of infectious diseases. In this study, BALB/c mice were exposed to low-dose UVB (250 J/m(2)) from Dermaray M-DMR-100 for 4 consecutive days. Twelve hours after the last UV exposure, groups of mice were injected with 2 × 10(6) Leishmania amazonensis promastigotes. The development of skin lesions, as assessed by measurement of visible cutaneous lesions, was significantly suppressed in low-dose UVB-irradiated mice compared to nonirradiated controls. In order to characterize the cytokines involved in this phenomenon, BALB/c mice were irradiated with identical doses of UVB, and gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin 4 cytokine levels in blood serum and skin were examined at different times by a sandwich enzyme-linked immunosorbent assay, immunohistochemical analysis, and reverse transcription (RT)-PCR. Upregulated expression of serum IFN-γ and TNF-α was observed from 6 to 24 h. Positive results for IFN-γ and TNF-α in UVB-irradiated mice were obtained by immunohistochemical analysis. By RT-PCR, the mRNA expression of both IFN-γ and TNF-α cytokines was detected in a time-dependent manner only in UVB-irradiated mice. Histopathological analysis and electron microscopy revealed that cellular infiltration, tissue parasitism, and parasitophorus vacuoles in irradiated mice were markedly less noticeable than those in nonirradiated controls. These results suggested that low-dose UVB irradiation played a pathogen-suppressing role in Leishmania-susceptible BALB/c mice via systemic and local upregulation of Th1 (IFN-γ and TNF-α) cytokines