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MiR-331-3p Inhibits Proliferation and Promotes Apoptosis of Nasopharyngeal Carcinoma Cells by Targeting elf4B-PI3K-AKT Pathway.

ABSTRACT: BACKGROUND:The incidence of nasopharyngeal carcinoma is increasing gradually, but the pathogenesis is not completely clear. MicroRNA, a highly conserved endogenous noncoding small molecule RNA, plays an essential role in the regulation of gene expression and is a hotspot in cancer research worldwide. OBJECTIVES:Although previous studies have confirmed that the abnormal expression of microRNAs is closely related to the progression of nasopharyngeal carcinoma, the role of miRNA-331-3p in nasopharyngeal carcinoma has not been studied. The purpose of this study was to explore the role and mechanism of miRNA-331-3p in the progression of nasopharyngeal carcinoma. MATERIALS AND METHODS:Real-time quantitative reverse transcription polymerase chain reaction was performed to detect the expression of miRNA-331-3p in nasopharyngeal carcinoma clinical samples and cell lines (CNE-1 and 5-8F cells). After overexpression of miRNA-331-3p in CNE-1 cells, cell proliferation was measured by Cell Counting Kit-8 assay, cell invasion was detected by Transwell assay, and apoptosis was tested by flow cytometry. In addition, the dual-luciferase reporter assay was used to identify the target gene of miRNA-331-3p and Western blotting was performed to measure the relative protein expression. RESULTS:The expression of miRNA-331-3p in nasopharyngeal carcinoma clinical samples and cells was decreased significantly. Overexpression of miRNA-331-3p markedly inhibited the proliferation and invasion of CNE-1 cells and promoted cell apoptosis. Moreover, overexpression of miRNA-331-3p reduced the expression of target gene elF4B, leading to inhibition of the phosphorylation of Phosphoinositide 3-kinase (PI3K) and Serine/ threonine kinase (AKT). CONCLUSION:miRNA-331-3p inhibited cell proliferation and induced cell apoptosis in nasopharyngeal carcinoma by targeting elF4B gene and then blocked the PI3K-AKT signaling pathway. SIGNIFICANCE:The role of miRNA-331-3p in the development of NPC and its mechanism provide new ideas for the treatment of nasopharyngeal carcinoma.

SUBMITTER: Xuefang Z

PROVIDER: S-EPMC6985969 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Objective:Mounting research has established the role of microRNAs (miRNAs) as oncogenes or anti-oncogenes (tumor suppressors) in the development and progression of several cancers. The purpose of our current study is to delineate the roles and functional mechanisms of miR-331-3p and MLLT10 in non-small cell lung cancer (NSCLC) tumorigenesis. Patients and Methods:Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was employed to measure miR-331-3p expression levels in twenty-six matched tumor tissues and non-cancerous tissues collected from patients suffering from NSCLC, and from six NSCLC cell lines separately: A549, H1650, H292, H1299, H1944 and BEAS-2b. We employed the dual-luciferase activity assay to check whether the putative gene, MLLT10, was a downstream target of miR-331-3p in NSCLC pathogenesis and development. Western blot was conducted to analyze the protein expression levels of MLLT10 (AF10), E-cadherin, Vimentin, and GAPDH. CCK-8 assay, transwell migration assay, and transwell invasion assay were carried out to observe the functions of miR-331-3p and MLLT10 on NSCLC tumor cell proliferation, metastasis, and invasion, respectively. To identify whether the metastasis of NSCLC tumor cells was EMT-mediated, supplementary experiments involving E-cadherin and Vimentin were implemented. Results:miR-331-3p was downregulated in NSCLC, which promoted tumor cell proliferation, whereas the overexpression of miR-331-3p inhibited tumor cell proliferation. Being a direct target of miR-331-3p, MLLT10 was negatively modulated by miR-331-3p, which suppressed tumor cell proliferation, migration, and invasion in NSCLC. However, MLLT10 overexpression alleviated the above inhibitory effects. Furthermore, EMT-mediated metastasis was proved to be present in NSCLC. Conclusion:miR-331-3p played a suppressor role in NSCLC tumor cell proliferation, EMT-mediated metastasis, and invasion by targeting MLLT10. Our findings highlighted that miR-331-3p/MLLT10 axis could be useful as a clinical diagnostic marker and therapeutic target in NSCLC patients.

Project description:BackgroundmiR-100 has been reported to closely associate with gastric cancer (GC) initiation and progression. However, the underlying mechanism of miR-100-3p in GC is still largely unclear. In this study, we intend to study how miR-100-3p regulates GC malignancy.MethodsThe expression levels of miR-100-3p in vitro (GES-1 and GC cell lines) and in vivo (cancerous and normal gastric tissues) were examined by quantitative real-time PCR (qRT-PCR). MTT and PE/Annexin V analyses were responsible for measurement of the effects of miR-100-3p on GC cell proliferation and apoptosis. Transwell assay with or without matrigel was used to examine the capacity of migration and invasion in GC cells. The interaction of miR-100-3p with bone morphogenetic protein receptor 2 (BMPR2) was confirmed through transcriptomics analysis and luciferase reporter assay. qRT-PCR and Western blot analyses were applied to determine the expression of ERK/AKT and Bax/Bcl2/Caspase3, which were responsible for the dysfunction of miR-100-3p.ResultsmiR-100-3p was down-regulated in GC cell lines and cancerous tissues, and was negatively correlated with BMPR2. Loss of miR-100-3p promoted tumor growth and BMPR2 expression. Consistently, the effects of miR-100-3p inhibition on GC cells were partially neutralized by knockdown of BMPR2. Over-expression of miR-100-3p simultaneously inhibited tumor growth and down-regulated BMPR2 expression. Consistently, over-expression of BMPR2 partially neutralized the effects of miR-100-3p over-expression. Further study demonstrated that BMPR2 mediated the effects downstream of miR-100-3p, which might indirectly regulate ERK/AKT and Bax/Bcl2/Caspase3 signaling pathways.ConclusionmiR-100-3p acted as a tumor-suppressor miRNA that down-regulated BMPR2, which consequently inhibited the ERK/AKT signaling and activated Bax/Bcl2/Caspase3 signaling. This finding provided novel insights into GC and could contribute to identify a new diagnostic and therapeutic target.

Project description:PURPOSE:Triple-negative breast cancer is characterized by fast progression with high possible for metastasis and poor survival. Dysfunction of microRNAs plays an important role in the initiation and progression of cancer. Our previous microRNA-seq data indicated the downregulation of miR-331-3p in triple-negative breast cancer tissues compared with that of the noncancer tissues. However, the function of miR-331-3p in triple-negative breast cancer remains largely unknown. Herein, the involvement of miR-331-3p in triple-negative breast cancer was investigated and the therapeutic potential of miR-331-3p was also explored. METHODS:Real-time quantitative polymerase chain reaction was performed to detect the expression of miR-331-3p in triple-negative breast cancer tissues and cell lines. The cell proliferation was determined by the cell counting kit-8 assay. Apoptosis of triple-negative breast cancer cells was examined by annexin V/propidium iodide staining. miRDB database was used to predict the potential targets of miR-331-3p. Western blot was performed to examine the expression of the target protein. RESULTS:miR-331-3p was significantly downregulated in triple-negative breast cancer tissues and cell line. Lower miR-331-3p expression was significantly correlated with the tumor size, TNM stage, and lymph node metastasis of patients with triple-negative breast cancer. Functional experiments showed that the overexpression of miR-331-3p inhibited the proliferation and increased apoptosis of triple-negative breast cancer cells. Neuropilin-2 was identified as a target of miR-331-3p, which harbored binding site of miR-331-3p in its 3'-untranslated region. Overexpression of miR-331-3p decreased the messenger RNA and protein levels of neuropilin-2 in triple-negative breast cancer cells. Restoration of neuropilin-2 partially reversed the inhibitory effects of miR-331-3p on the proliferation of triple-negative breast cancer cells. CONCLUSIONS:Our results demonstrated the novel function of miR-331-3p/neuropilin-2 signaling in regulating the malignant behaviors of triple-negative breast cancer cells, which suggested miR-331-3p as a potential target for the treatment of triple-negative breast cancer.

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MiR-331-3p Inhibits Proliferation and Promotes Apoptosis of Nasopharyngeal Carcinoma Cells by Targeting elf4B-PI3K-AKT Pathway.

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