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?icroRNA?421 promotes the progression of non?small cell lung cancer by targeting HOPX and regulating the Wnt/??catenin signaling pathway.

ABSTRACT: MicroRNAs (miRNAs) function as key regulators of numerous types of cancers. miRNA (miR)?421 expression is dysregulated in a variety of tumors; however, its role in non?small cell lung cancer (NSCLC) remains unclear. In the present study, the role and molecular mechanism of miR?421 in NSCLC was investigated. In this study, miRNA (miR)?421 was upregulated in NSCLC tissues and cell lines used the reverse transcriptase quantitative polymerase chain reaction. Ectopic expression of miR?421 significantly promoted cell proliferation in vitro and tumor growth in vivo by promoting cell cycle progression via CCK-8, colony formation, EdU assay, xenograft model and cell cycle assay. In addition, miR?421 inhibited NSCLC cell apoptosis by flow cytometry apoptosis assay, as evidenced by anti?apoptosis gene Bcl?2 and apoptosis gene cleaved caspase?3 and cleaved PARP using western blot assay. Furthermore, miR?421 promoted cell migration and invasion through EMT process using Transwell and western blot assay. It was also demonstrated that miR?421 can directly target HOPX by the EGFP reporter assay and western blot assay. MiR?421 overexpression promoted the protein expression levels of ??catenin, cyclin D1 and c?myc by western blot assay, which are the downstream genes of Wnt pathway. These data indicated that miR?421 may act as an oncogene through the effects of HOPX on the Wnt/??catenin signaling pathway and may provide insight into the mechanisms underlying carcinogenesis and the identification of potential biomarkers associated with NSCLC.

SUBMITTER: Liang H

PROVIDER: S-EPMC6580023 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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ΜicroRNA‑421 promotes the progression of non‑small cell lung cancer by targeting HOPX and regulating the Wnt/β‑catenin signaling pathway.

Liang Huagang H Wang Chao C Gao Kun K Li Jian J Jia Rui R

Molecular medicine reports 20190509 1

MicroRNAs (miRNAs) function as key regulators of numerous types of cancers. miRNA (miR)‑421 expression is dysregulated in a variety of tumors; however, its role in non‑small cell lung cancer (NSCLC) remains unclear. In the present study, the role and molecular mechanism of miR‑421 in NSCLC was investigated. In this study, miRNA (miR)‑421 was upregulated in NSCLC tissues and cell lines used the reverse transcriptase quantitative polymerase chain reaction. Ectopic expression of miR‑421 significant ...[more]

PMID: 31115507

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Project description:BackgroundWnt2 is overexpressed and able to promote tumorigenesis in many types of cancer. However, its expression and role in lung cancer has not been well clarified yet. In this study, we aims to investigate the expression pattern, clinical significance and the underlying molecular mechanism of Wnt2 in non-small lung cancer (NSCLC).MethodsImmunohistochemical staining and ELISA assays were applied to detect Wnt2 level in tumor tissue and serum. EDU incorporation assays and colony formation assays were used to evaluate the growth-promoting effect of Wnt2 in vitro. Then we performed western blot and immunofluorescence assays to detect the activation of WNT signaling pathway. Finally mice engrafted with NSCLC tumor cells were used to assess the role of Wnt2 in vivo.ResultsImmunohistochemical staining consisting of 264 NSCLC tumor tissues showed that a high level of Wnt2 was associated with a poor overall survival (OS) and relapse-free survival (RFS) of NSCLC patients (P = 0.002 and 0.0005, respectively). Multivariate analysis presented that Wnt2 level in tumor tissue was an independent prognostic factor (P = 0.049 for OS and P = 0.002 for RFS, respectively). Furthermore, ELISA assays for 181 individuals (116 NSCLC and 65 controls) revealed that serum Wnt2 levels in adenocarcinoma was significantly higher than that in healthy volunteers (P < 0.0001). In vitro H460 cell line stably overexpressing Wnt2 showed enhanced growth activity than the control cells whereas knockdown of Wnt2 by siRNA in H1299 cells resulted in decreased growth activity. Additionally, Wnt2 level in tumor tissues was significantly associated with Ki-67 level (rs: 0.316; P < 0.0001). Immunofluorescence and Western blot assays detected the translocation of β-catenin from cytoplasm into nucleus, which indicated that Wnt2 probably promotes proliferation by activating WNT/β-catenin pathway. In vivo H460 cells expressing exogenous Wnt2 showed increased growth-promoting effect in Balb/c nude mice than control cells.ConclusionsThe present study for the first time suggested that Wnt2 was both a prognostic and a diagnostic biomarker for NSCLC. Tumor-derived Wnt2 can promote growth activity of NSCLC cells through activating WNT/β-catenin signaling pathway.

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?icroRNA?421 promotes the progression of non?small cell lung cancer by targeting HOPX and regulating the Wnt/??catenin signaling pathway.

Publications

ΜicroRNA‑421 promotes the progression of non‑small cell lung cancer by targeting HOPX and regulating the Wnt/β‑catenin signaling pathway.

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