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MicroRNA-98-5p regulates the proliferation and apoptosis of A549 cells by targeting MAP4K3.

ABSTRACT: Non-small cell lung cancer (NSCLC) is a primary subtype of lung cancer that is accompanied by a high incidence rate and poor prognosis. The primary treatment for NSCLC is chemotherapy, which has low effectiveness and high toxicity. Thus, novel targeted therapy has drawn much attention in recent years. MicroRNAs (miRs) serve important roles in multiple cancer types. In the current study, a decrease in miR-98-5p and an increase in mitogen-activated protein kinase kinase kinase kinase 3 (MAP4K3) was observed in NSCLC tumor tissues compared with normal tissues. miR-98-5p was predicted to target positions 1,056-1,063 of the MAP4K3 3'-untranslated region (UTR). The binding sites between miR-98-5p and the 3'-UTR of MAP4K3 messenger RNA were supported by the results of a dual-luciferase reporter assay. Compared with the control and miR-negative control (NC) groups, miR-98-5p mimic significantly reduced cell proliferation and increased apoptosis in NSCLC cells. In addition, miR-98-5p mimic reduced the expression of MAP4K3 and mammalian target of rapamycin while increasing the expression of cleaved caspase-3 compared with the control group and miR-NC groups. In conclusion, miR-98-5p may inhibit the progression of NSCLC via targeting of MAP4K3.

SUBMITTER: Wang Z

PROVIDER: S-EPMC6757256 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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MicroRNA-98-5p regulates the proliferation and apoptosis of A549 cells by targeting MAP4K3.

Wang Ziquan Z Han Zhengxiang Z Zhang Lansheng L Zhang Shiqiang S Wang Baoqing B

Oncology letters 20190822 4

Non-small cell lung cancer (NSCLC) is a primary subtype of lung cancer that is accompanied by a high incidence rate and poor prognosis. The primary treatment for NSCLC is chemotherapy, which has low effectiveness and high toxicity. Thus, novel targeted therapy has drawn much attention in recent years. MicroRNAs (miRs) serve important roles in multiple cancer types. In the current study, a decrease in miR-98-5p and an increase in mitogen-activated protein kinase kinase kinase kinase 3 (MAP4K3) wa ...[more]

PMID: 31579095

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Project description:Although deregulated circulatory miRNA signatures during diabetes have been identified for some years now, the effects of such miRNAs on several target tissues are not yet thoroughly investigated. The skin that is nourished by components present in the circulation exhibits several notable abnormal features during diabetes. We, therefore, hypothesized that such altered circulatory miRNA levels might be critical in the onset and progression of impaired skin health during diabetes. RNA sequencing from blood samples of normal and type 2 diabetic human subjects identified 9 upregulated and 19 downregulated miRNAs. miR-98-5p was significantly downregulated and its overexpression down-regulated PPP1R15B levels in HaCaT cells and this was prevented by the miR-98-5p inhibitor. This was validated in human primary epidermal keratinocytes and further supported by a dual reporter luciferase assay of the PPP1R15B 3'UTR where miR-98-5p significantly decreased the luciferase activity which was prevented in the presence of the miRNA inhibitor and by mutation in the miRNA binding site. By targeting PPP1R15B, miR-98-5p increases levels of p-eIF2α, BiP and CHOP. Consequently, there was induction of apoptosis accompanied with decreased proliferation in the presence of miR-98-5p. Conversely, miR-98-5p inhibition alone inhibited apoptosis and promoted proliferation. Taken together, our data suggest that by targeting PPP1R15B, miR-98-5p induces apoptosis and decreases proliferation. As opposed to this since circulatory miR-98-5p levels are decreased in diabetes, we believe that this decrease in the circulation that feeds the skin layers might be a major contributor of hyperproliferation as seen in the skin during diabetes.Abbreviations: miRNAs: MicroRNAs; PPP1R15B: PPP1R15B: Protein Phosphatase 1 Regulatory Subunit 15B; TGFβR1: Transforming Growth Factor Beta Receptor 1; ER: Endoplasmic Reticulum; Bip: Binding Immunoglobulin Protein; Chop: CCAAT-enhancer-binding protein homologous protein; p-eIF2α: Eukaryotic Translation Initiation Factor 2a; Bax: Bcl2-associated X protein; Bcl-2: B-cell CLL/lymphoma 2; PCNA: Proliferating Cell Nuclear Antigen; K5: Cytokeratin 5; qRT-PCR: Quantitative Real-Time PCR; ESCC: Oesophageal squamous cell carcinoma; HCC: Hepatocellular carcinoma; CTHRC1: Collagen triple helix repeat containing 1; SALL4: Sal-like protein 4; TNFα: Tumour Necrosis Factor alpha; PGC-1β: Peroxisome Profilerator-activated receptor-γ coactivator-1β; IGF2BP1: Insulin-like growth factor 2 mRNA binding protein 1.

Dataset Information

MicroRNA-98-5p regulates the proliferation and apoptosis of A549 cells by targeting MAP4K3.

Publications

MicroRNA-98-5p regulates the proliferation and apoptosis of A549 cells by targeting MAP4K3.

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