Functional significance of the long non-coding RNA RP11-169D4.1 as a metastasis suppressor in laryngeal squamous cell carcinoma by regulating CDH1.

The present study investigated the expression profile and the function of RP11-169D4.1 and explored its potential mechanisms in laryngeal squamous cell carcinoma. The biological function of RP11-169D4.1 was examined using the MTT assay, flow cytometric analysis, wound healing and transwell assays. The relationship between RP11-169D4.1 and miR-205-5p was discovered by Argonaute 2 protein immunoprecipitation. The target gene of RP11-169D4.1 was CDH1 which was assessed by Pearson's correlation analysis, RT-PCR and western blot assay. We demonstrated that RP11-169D4.1 expression was markedly decreased in LSCC tissues and cell lines. The overexpression of RP11-169D4.1 inhibited the proliferation, migration and invasion of LSCC cell lines as well as promoted apoptosis. We further verified that miR-205-5p had binding sites with RP11­169D4.1 and that RP11-169D4.1 could regulate the expression of CDH1. Ectopic transfection of RP11-169D4.1 led to a significant reduction in the downstream signaling molecule AKT in LSCC cells. The long non-coding RNA RP11-169D4.1 may serve as a tumor suppressor and a promising therapeutic target in laryngeal cancer, which could inhibit the process of EMT by regulating CDH1.

Epstein-Barr virus encoded microRNA BART7 regulates radiation sensitivity of nasopharyngeal carcinoma.

Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is very sensitive to radiotherapy. To date, the underlying mechanism remains poorly understood. Here, we demonstrated that expression of EBV-encoded microRNA BART7 (ebv-miR-BART7) increases responsiveness of NPC to radiation treatment by targeting GFPT1/TGFß1 signaling. GFPT1 is the the key rate-limiting enzyme of the hexosamine signaling pathway and governs TGFß1 production. TGFß1, a pleotropic cytokine with the potency to trigger self-renewal and damage-repair machinery in somatic cells. TGFß1 can protect zebrafish embryo from the lethal effects of radiation treatment. In silico analysis showed that ebv-miR-BART7 could target GFPT1 transcript. Correlation analysis on primary NPC tissues suggested that ebv-miR-BART7 and GFPT1 have negative expression correlation. Expression of GFPT1 and TGFß1 were inducible by radiation in NPC cell with ebv-miR-BART7 expression. Further, suppressing endogenous GFPT1 expression inhibited TGFß1 which subsequently increased the responsiveness of NPC to radiation treatment. Taken together, our results demonstrated that ebv-miR-BART7 controls TGFß1 production by targeting GFPT1. Detection of ebv-miR-BART7 may provide useful indicator for monitoring NPC progression and predict therapeutic outcomes.

Comparison of CT and MRI in Diagnosis of Laryngeal Carcinoma with Anterior Vocal Commissure Involvement.

This study aimed to compare the accuracy of CT and MRI in determining the invasion of thyroid cartilage by and the T staging of laryngeal carcinoma with anterior vocal commissure (AVC) involvement. A total of 26 cases of laryngeal carcinomas with AVC involvement from May 2012 to January 2014 underwent enhanced CT and MRI scan, out of whom 6 patients also underwent diffusion-weighted magnetic resonance imaging(DWI). T staging and thyroid cartilage involvement were evaluated. All the surgical specimens underwent serial section and were reviewed by two senior pathologists independently. When compared with pathologic staging, the accuracy was 88.46% (23/26) of MRI scan (with a 95% confidence interval 37~77%) and 57.69% (15/26) of CT scan (with a 95% confidence interval 70~98%), respectively (P < 0.01). We also reported three cases who were misdiagnosed on CT or MRI about either the thyroid cartilage was involved or not, and one case of preliminary study of DWI. Compared to CT, MRI exhibited a higher accuracy rate on T staging of laryngeal carcinomas with AVC involvement. Combined utility of CT and MRI could help improve the accuracy of assessment of thyroid cartilage involvement and T staging of laryngeal carcinomas with AVC involvement.

Epigenetic dysregulation in laryngeal squamous cell carcinoma.

Laryngeal carcinoma is a common head and neck cancer with poor prognosis. Patients with laryngeal carcinoma usually present late leading to the reduced treatment efficacy and high rate of recurrence. Despite the advance in the use of molecular markers for monitoring human cancers in the past decades, there are still no reliable markers for use to screen laryngeal carcinoma and follow the patients after treatment. Epigenetics emerged as an important field in understanding the biology of the human malignancies. Epigenetic alterations refer to the dysregulation of gene, which do not involve the alterations of the DNA sequence. Major epigenetic changes including methylation imbalance, histone modification, and small RNA dysregulation could play a role in the development of human malignancies. Global epigenetic change is now regarded as a molecular signature of cancer. The characteristics and behavior of a cancer could be predicted based on the specific epigenetic pattern. We here provide a review on the understanding of epigenetic dysregulation in laryngeal carcinoma. Further knowledge on the initiation and progression of laryngeal carcinoma at epigenetic level could promote the translation of the knowledge to clinical use.