Dataset Information

Hsa-miR-301a-3p Acts as an Oncogene in Laryngeal Squamous Cell Carcinoma via Target Regulation of Smad4.

ABSTRACT: Laryngeal squamous cell carcinoma (LSCC) is the second most common malignant head and neck squamous cell carcinoma. Exploring the molecular indicators of malignant behavior will enhance our knowledge of this type cancer and provide novel options for its prevention, diagnosis, and treatment. MicroRNA might exert regulatory roles as oncogenes or anti-oncogenes. We studied the expression of miR-301a-3p in LSCC tissues and cell lines and conducted a functional analysis of miR-301a-3p to confirm if miR-301a-3p functions as an oncogene in LSCC. We found Smad4 to be one of the potential target genes of miR-301a-3p, and it functioned as a tumor suppressor in LSCC. Hsa-miR-301a-3p participated in the epithelial-mesenchymal transition (EMT) process, which is considered to be linked to the process of LSCC development. Our present findings indicate that miR-301a-3p acts as an oncogene by directly regulating the anti-oncogene Smad4, thereby playing a role in the occurrence and development of LSCC. The present findings are expected to help in the development of novel targets for the prevention and treatment of LSCC.

SUBMITTER: Lu Y

PROVIDER: S-EPMC4643083 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Hsa-miR-301a-3p Acts as an Oncogene in Laryngeal Squamous Cell Carcinoma via Target Regulation of Smad4.

Lu Yan Y Gao Wei W Zhang Chunming C Wen Shuxin S Huangfu Hui H Kang Jian J Wang Binquan B

Journal of Cancer 20151020 12

Laryngeal squamous cell carcinoma (LSCC) is the second most common malignant head and neck squamous cell carcinoma. Exploring the molecular indicators of malignant behavior will enhance our knowledge of this type cancer and provide novel options for its prevention, diagnosis, and treatment. MicroRNA might exert regulatory roles as oncogenes or anti-oncogenes. We studied the expression of miR-301a-3p in LSCC tissues and cell lines and conducted a functional analysis of miR-301a-3p to confirm if m ...[more]

PMID: 26640587

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Project description:BACKGROUND:Treatments that target cancer stem cells play an important role in the controlling and eliminating of tumor initiation as well as in development, progression, and chemotherapy/radiotherapy resistance. In our previous study, we cultured and harvested human laryngeal cancer stem cells (CSCs) and applied microRNA biochips to screen differentially expressed miRNAs that were related to radiation tolerance in irradiated human laryngeal CSCs. According to the predicted genes and pathways of differential miRNAs target, down-regulated expression of hsa-miR-138-2-3p under radiation was thought to play a key role in enhancing the radio-sensitivity in human laryngeal squamous cancer stem cells. METHOD:To investigate the radiational enhancement of hsa-miR-138-2-3p, we transfected hsa-miR-138-2-3p mimics that were synthesized based on the sequences of hsa-miR-138-2-3p in vitrointo human laryngeal CSCs (Hep-2, M2e, and TU212 cell lines) to make hsa-miR-138-2-3p overexpressed, and the tumorous specialities of CSCs, like cell proliferation, invasion, apoptosis, cell cycle arrest, and DNA damage were evaluated by CCK-8 assay, clone formation assay, invasion assay, flow cytometry, and comet assay. Furthermore, we explored the signal transduction pathways that regulated the cancer stem cell initiation, development, invasion, apoptosis and cell cycle arrest, which were controlled by hsa-miR-138-2-3p. RESULT:Overexpressed hsa-miR-138-2-3p played a key role in many anti-cancer biological processes in human laryngeal CSCs: (1) it decreased laryngeal CSCs proliferation and invasion in response to radiotherapy; (2) it increased the proportion of early and late apoptosis in laryngeal CSCs after radiation, raised G1 phase arrest in laryngeal CSCs after radiation, and decreased the proportion of S stage cells of cell cycle that were related to radio-resistance in laryngeal CSCs; (3) it down-regulated the expression of ?-catenin in Wnt signal pathway that was related to the tolerance of laryngeal CSCs to radiotherapy; (4) it down-regulated the expression of YAP1 in Hippo signal pathway that regulated cell proliferation, invasion and apoptosis; (5) it up-regulated the expression of p38 and JNK1 in MAPK signal pathway that was concerned to radio-sensitivity. CONCLUSION:In the present study, it was found that hsa-miR-138-2-3p regulated the Wnt/?-catenin pathways, the Hippo/YAP1 pathways, and the MAPK/p38/JNK1 pathways that were involved in cell proliferation, invasion, apoptosis, cell cycle arrest, radio-resistance and radio-sensitivity in laryngeal CSCs. These results will be useful for a better understanding of the cell biology of hsa-miR-138-2-3p in laryngeal CSCs, and for serving hsa-miR-138-2-3p as a promising biomarker and as a target for diagnosis and for novel anti-cancer therapies for laryngeal cancers.

Project description:Purpose:Long noncoding RNAs (lncRNAs) have been identified as an important class of noncoding RNAs that are deeply involved in multiple biological processes in tumorigenesis. This study is to investigate the critical roles and biological function of lncRNA growth arrest-specific 5 (GAS5) in tumorigenesis of laryngeal squamous cell carcinoma (LSCC). Patients and methods:A total of 59 samples of LSCC and paired adjacent tissue, as well as corresponding clinicopathological information were collected. GAS5 expression in both LSCC tissues and human SUN1076 and SNU899 cell lines were analyzed by Real-time quantitative RT-PCR method. Ectopic expression of GAS5 by vector transfection in LSCC cell lines and followed by in vitro experiments was to investigate the critical roles and function of GAS5 in LSCC. Cell Counting Kit 8 (CCK8) assay and PE/7AAD Annexin V Apoptosis analysis was to evaluate cell proliferation ability and cell apoptosis. Co-transfection of GAS5 and miR-21 was to explore the interaction between GAS5 and miR-21 in LSCC. BAX and CDK6 protein level were analyzed by western blot method. Results:This study demonstrated that GAS5 was significantly downregulated in LSCC tissue and human LSCC cell lines. GAS5 levels were correlated with the clinicopathological features of LSCC patients. In addition, the ectopic expression of GAS5 significantly inhibited cell proliferation and promoted apoptosis. Co-expression analyses indicated that GAS5 is negatively correlated with miR-21 in LSCC tissues. Overexpression of miR-21 eliminated GAS5-mediated cell apoptosis and proliferation suppression. Furthermore, GAS5, which upregulated BAX mRNA expression and downregulated CDK6 mRNA expression, was reversed by ectopic expression of miR-21. Conclusion:GAS5 suppresses LSCC progression through the negative regulation of miR-21 and its targets involved in cell proliferation and apoptosis, indicating that GAS5 may serve as a biomarker and potential target for LSCC therapy.

Project description:Background: Circular RNAs (circRNAs) have been discovered to participate in the carcinogenesis of multiple cancers. However, the role of circRNAs in esophageal squamous cell carcinoma (ESCC) progression is yet to be properly understood. This research aimed to investigate and understand the mechanism used by circRNAs to regulate ESCC progression.Methods: Bioinformatics analysis was first performed to screen dysregulated circRNAs and differentially expressed genes in ESCC. The ESCC tissue samples and adjacent normal tissue samples utilized in this study were obtained from 36 ESCC patients. All the samples were subjected to qRT-PCR analysis to identify the expression of TXNRD1, circRNAs, and miR-1305. Luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay were later conducted to verify the existing relationship among circ0120816, miR-1305 and TXNRD1. CCK-8, BrdU, cell adhesion, cell cycle, western blot and caspase 3 activity assays were also employed to evaluate the regulation of these three biological molecules in ESCC carcinogenesis. To evaluate the effect of circ0120816 on ESCC tumor growth and metastasis, the xenograft mice model was constructed.Results: Experimental investigations revealed that circ0120816 was the highest upregulated circRNA in ESCC tissues and that this non-coding RNA acted as a miR-1305 sponge in enhancing cell viability, cell proliferation, and cell adhesion as well as repressing cell apoptosis in ESCC cell lines. Moreover, miR-1305 was observed to exert a tumor-suppressive effect in ESCC cells by directly targeting and repressing TXNRD1. It was also noticed that TXNRD1 could regulate cyclin, cell adhesion molecule, and apoptosis-related proteins. Furthermore, silencing circ0120816 was found to repress ESCC tumor growth and metastasis in vivo.Conclusions: This research confirmed that circ0120816 played an active role in promoting ESCC development by targeting miR-1305 and upregulating oncogene TXNRD1.

Dataset Information

Hsa-miR-301a-3p Acts as an Oncogene in Laryngeal Squamous Cell Carcinoma via Target Regulation of Smad4.

Publications

Hsa-miR-301a-3p Acts as an Oncogene in Laryngeal Squamous Cell Carcinoma via Target Regulation of Smad4.

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