LINC00958 Promotes The Malignancy Of Nasopharyngeal Carcinoma By Sponging microRNA-625 And Thus Upregulating NUAK1.

PURPOSE: The aberrant expression of long noncoding RNAs (lncRNAs) indicates progression of various diseases. LINC00958 has been well studied in several types of human cancer; however, the expression profile, functions, and potential mechanism of action of this lncRNA in nasopharyngeal carcinoma (NPC) remain largely unclear and still need to be elucidated. In the present study, we aimed to measure LINC00958 expression in NPC, determine its clinical value, and explore its roles in NPC progression as well as the mechanisms behind these processes. METHODS: The expression profile of LINC00958 in NPC was evaluated by reverse-transcription quantitative polymerase chain reaction (RT-qPCR). A series of functional assays, including the Cell Counting Kit-8 assay, flow cytometry, a Transwell assay, and an in vivo nude mouse model, were utilized to determine the participation of LINC00958 in the malignancy of NPC. RESULTS: LINC00958 was found to be upregulated in NPC tissue specimens and cell lines. The LINC00958 overexpression significantly correlated with tumor size, lymph node status, TNM stage, and worse overall survival among NPC patients. Downregulation of LINC00958 suppressed NPC cell proliferation, migration, and invasion and induced apoptosis in vitro. Additionally, the LINC00958 knockdown impaired tumor growth in vivo. Mechanistically, LINC00958 was found to serve as a molecular sponge of microRNA-625 (miR-625), thereby upregulating NUAK family SNF1-like kinase 1 (NUAK1) in NPC cells. Lastly, rescue experiments validated the involvement of the miR-625-NUAK1 axis in LINC00958-mediated biological functions in NPC. CONCLUSION: Our results demonstrated that LINC00958 works as an oncogene in NPC and plays a key role in the malignant phenotype of NPC cells by sponging miR-625 and increasing NUAK1 expression. The LINC00958-miR-625-NUAK1 pathway might be a target for anticancer therapy in patients with NPC.

miR-93 enhances cell proliferation by directly targeting CDKN1A in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy of the head and neck with the highest incidence rate in southern China. The aim of the present study was to understand the molecular mechanisms that underlie the progression of NPC. The relative expression of miR-93 and CDKN1A was detected by the reverse-transcription quantitative PCR. Western blot analysis was applied to detect the protein levels of genes. Luciferase activity report was applied to verify the target of miRNA. Cell growth was assayed by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. miR-93 was upregulated in NPC tissues and cell lines compared with normal samples. Re-expression of miR-93 promoted cell growth in vitro as determined by the MTT assay. CDKN1A was identified by luciferase reporter as a direct target of miR-93. Its expression was downregulated by miR-93. Furthermore, the results showed that the expression of miR-93 was inversely correlated with the expression of CDKN1A protein. miR-93 enhanced cell proliferation in NPC by directly targeting CDKN1A. It is suggested that miR-93/CDKN1A axis may present a new target for the treatment of NPC.

G1/S-specific cyclin-D1 might be a prognostic biomarker for patients with laryngeal squamous cell carcinoma.

OBJECTIVE: To investigate the prognostic role of antigen KI-67 (Ki-67) and G1/S-specific cyclin-D1 (cyclin-D1) in patients with laryngeal squamous cell carcinoma (LSCC). METHODS: Immunohistochemical staining (IHS) was used to determine the protein expression of Ki-67 and cyclin-D1 in LSCC tissues. Kaplan-Meier survival curves was calculated with reference to Ki-67 and cyclin-D1 levels. RESULTS: Cyclin-D1 and Ki67 were expressed in the nuclei of cancer cells. Among the total of 92 cancer tissues examined by immunohistochemistry, 60 (65.22%) had cyclin-D1 overexpression and 56 (60.87%) had Ki67 overexpression. Cyclin-D1 overexpression is associated with the advanced stage of the cancer (P=0.029), but not with gender, age, stage of cancer, histological differentiation, anatomical site, smoking history and alcohol consumption history. Ki67 overexpression is not associated with the advanced stage, gender, age, histological differentiation, anatomical site, smoking history and alcohol consumption history. A statistically significant correlation was found between lymph node status and the expression of Ki67 (p=0.025). Overexpression of cyclin-D1 was correlated to shorter relapse-free survival period (P<0.001). CONCLUSIONS: Overexpression of cyclin-D1 can be used as a marker to predict relapse in patients with LSCC after primary curative resection.