MMP1 Overexpression Promotes Cancer Progression and Associates with Poor Outcome in Head and Neck Carcinoma.

Matrix metalloproteinase-1 (MMP1) has been reported to play key roles in a variety of cancers by degrading the extracellular matrix. However, its carcinogenic roles have not been shown yet in head and neck squamous cell carcinoma (HNSCC). This study aimed to elucidate its expression pattern and functional roles as well as clinical significance in HNSCC. The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and immunohistochemistry (IHC) were utilized to determine the MMP1 expression pattern and the associations between its expression and patients' outcome in HNSCC. Mice tongue squamous cell carcinoma model induced by 4-nitroquinoline 1-oxide (4NQO) and siRNA-mediated cellular assay in vitro were utilized to evaluate the oncogenic role of MMP1. The biological functions and cancer-related pathways involved in MMP1-related genes were found through bioinformatics analysis. Both mRNA and protein abundance of MMP1 were highly increased in HNSCC as compared to its non-tumor counterparts. MMP1 overexpression positively correlated with advanced tumor size, cervical node metastasis, and advanced pathological grade and lower patients' survival. In the 4NQO-induced animal model, MMP1 expression increased along with the progression of the disease. In HNSCC cells, siRNA-mediated knockdown of MMP1 significantly inhibited cell proliferation, migration, and invasion and activated apoptosis and epithelia-mesenchymal transition (EMT). GSEA, GO, and KEGG analyses showed that MMP1 expression was significantly related to cancer-related pathways and cancer-related functions. Together, our results demonstrated MMP1 serves as a novel prognostic biomarker and putative oncogene in HNSCC.

Retraction Notice to: Silencing of lncRNA LINC00857 Enhances BIRC5-Dependent Radio-Sensitivity of Lung Adenocarcinoma Cells by Recruiting NF-κB1.

[This retracts the article DOI: 10.1016/j.omtn.2020.09.020.].

[Related factors of cervical lymph node metastasis and prognosis of patients with cN0 tongue squamous cell carcinoma].

PURPOSE: To explore the related factors of cervical lymph node metastasis and postoperative quality of life in patients with cN0 tongue squamous cell carcinoma (SCC), and provide a theoretical basis for clinical prediction of occult neck metastasis and improvement of survival rate. METHODS: A total of 283 patients with cN0 tongue SCC who underwent surgery in Huaian No.1 People's Hospital were collected. Chi-square test and logistic regression were used to analyze the correlation between cervical lymph node metastasis and clinical pathological parameters of patients. Single-factor and multi-factor Cox regression analysis were used to explore independent risk factors for prognosis of patients with tongue SCC. Survival analysis was used to study the correlation between cervical lymph node metastasis and prognosis of patients. SPSS 21.0 software package was used for statistical analysis. RESULTS: Chi-square test and logistic regression analysis showed that infiltration depth, T stage and pathological grade were closely related to cervical lymph node metastasis(P<0.05), and infiltration depth was the main factor leading to postoperative cervical lymph node metastasis(OR=2.175). The depth of invasion, pathological grade and cervical lymph node metastasis could be regarded as independent risk factor affecting the prognosis of patients with tongue SCC(P<0.05). CONCLUSIONS: Invasion depth, T stage and pathological grade can be used as indicators to predict occult cervical lymph node metastasis in patients with cN0 tongue SCC. Invasion depth, pathological grade and cervical lymph node metastasis can be used as independent indicators to predict the prognosis of patients with cN0 tongue SCC.

Silencing of lncRNA LINC00857 Enhances BIRC5-Dependent Radio-Sensitivity of Lung Adenocarcinoma Cells by Recruiting NF-κB1.

Lung adenocarcinoma (LUAD) is a predominant type of lung cancer in never-smoker patients. In this study, we identified a long noncoding RNA (lncRNA) LINC00857 that might regulate radio-sensitivity of LUAD cells. Expression of LINC00857 and baculoviral IAP repeat containing 5 (BIRC5) was determined to be upregulated in LUAD cells and tissues using qRT-PCR and western blot analysis. The correlation between LINC00857 and nuclear factor kappa B subunit 1 (NF-κB1) was verified using RNA immunoprecipitation and chromatin immunoprecipitation assays, while the binding relationship between NF-κB1 and BIRC5 was determined by dual-luciferase reporter assay. It was suggested that LINC00857 could recruit NF-κB1 in BIRC5 promoter region. BIRC5 promoter activity was repressed in response to small interfering-LINC00857 (si-LINC00857) in LUAD cells. Silencing LINC00857 or BIRC5 reduced proliferation and colony formation but enhanced apoptosis and radio-sensitivity of LUAD cells. The experiment in vivo verified the function of silencing LINC00857 on enhancing radio-sensitivity of LUAD cells. Our results reveal a functional regulatory LINC00857-NF-κB1-BIRC5 triplet in LUAD cells, suggesting LINC00857 as a potential target for LUAD treatment.

Exosomal microRNA-26b-5p down-regulates ATF2 to enhance radiosensitivity of lung adenocarcinoma cells.

Lung adenocarcinoma (LUAD), as the most common subtype of non-small cell lung cancer, is responsible for more than 500 000 deaths worldwide annually. In this study, we identify a novel microRNA-26b-5p (miR-26b-5p) and elucidated its function on LUAD. The survival rate of parent LUAD cells and radiation-resistant LUAD cells were determined using clonogenic survival assay. We overexpressed or inhibited miR-26b-5p in LUAD, and the correlation between activating transcription factor 2 (ATF2) and miR-26b-5p was determined using integrated bioinformatics analysis and dual-luciferase reporter gene assay. Exosomes derived from A549 cell lines were then detected using Western blot assay, followed by co-transfection with radiation-resistant A549R cells. LUAD tissues and serum were collected, followed by miR-26b-5p relative expression quantification using RT-qPCR. miR-26b-5p was identified as the most differentially expressed miRNA and was down-regulated in LUAD. Radiation-resistant cells were more resistant to X-radiation compared with parent cells. miR-26b-5p overexpression and X-irradiation led to enhanced radiosensitivity of LUAD cells. ATF2 was negatively targeted by miR-26b-5p. Exosomal miR-26b-5p derived from A549 cells could be transported to irradiation-resistant LUAD cells and inhibit ATF2 expression to promote DNA damage, apoptosis and radiosensitivity of LUAD cells, which was verified using serum-based miR-26b-5p. Our results show a regulatory network of miR-26b-5p on radiosensitivity of LUAD cells, which may serve as a non-invasive biomarker for LUAD.