miR-98 inhibits expression of TWIST to prevent progression of non-small cell lung cancers

Zhou, Haiyu; Huang, Zhizhou; Chen, Size

doi:10.1016/j.biopha.2017.01.012

Cited by 26 publications

(23 citation statements)

References 31 publications

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“…Recent studies have indicated the importance of miR-98 in colon 39 , lung 40 , liver 41 and prostate 42 cancer. Meta-analysis of six miRNA datasets revealed up-regulation of 15 miRNAs, miR-98 being one of them, in recurrent compared to non-recurrent prostate samples suggesting the predictive ability of miR-98 along with other miRNAs 42 .…”

Section: Discussionmentioning

confidence: 99%

A Plasma Biomarker Panel of Four MicroRNAs for the Diagnosis of Prostate Cancer

Matin

Jeet

Moya

et al. 2018

Sci Rep

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Prostate cancer is diagnosed in over 1 million men every year globally, yet current diagnostic modalities are inadequate for identification of significant cancer and more reliable early diagnostic biomarkers are necessary for improved clinical management of prostate cancer patients. MicroRNAs (miRNAs) modulate important cellular processes/pathways contributing to cancer and are stably present in body fluids. In this study we profiled 372 cancer-associated miRNAs in plasma collected before (~60% patients) and after/during commencement of treatment (~40% patients), from age-matched prostate cancer patients and healthy controls, and observed elevated levels of 4 miRNAs - miR-4289, miR-326, miR-152-3p and miR-98-5p, which were validated in an independent cohort. The miRNA panel was able to differentiate between prostate cancer patients and controls (AUC = 0.88). Analysis of published miRNA transcriptomic data from clinical samples demonstrated low expression of miR-152-3p in tumour compared to adjacent non-malignant tissues. Overexpression of miR-152-3p increased proliferation and migration of prostate cancer cells, suggesting a role for this miRNA in prostate cancer pathogenesis, a concept that was supported by pathway analysis of predicted miR-152-3p target genes. In summary, a four miRNA panel, including miR-152-3p which likely targets genes with key roles in prostate cancer pathogenesis, has the potential to improve early prostate cancer diagnosis.

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Section: Discussionmentioning

confidence: 99%

A Plasma Biomarker Panel of Four MicroRNAs for the Diagnosis of Prostate Cancer

Matin

Jeet

Moya

et al. 2018

Sci Rep

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“…In HCC, miR-98-5p downregulation stimulated malignant progression through several posttranslational targets, such as IGFBP1, CTHRC1 and SALL4 [ 10 , 30 , 31 ]. MiR-98-5p was significantly increased and promoted cell proliferation and invasion in lung cancer by directly targeting TWIST, PAK1, and ITGB3 [ 13 , 32 , 33 ]. Vinayakumar Siragam et al reported that miR-98 was involved in the regulation of cell survival, proliferation, tumorigenesis and angiogenesis via targeting ALK4 and MMP11 in breast cancer [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…Aberrantly expressed miRNAs have been reported to serve as tumor suppressors or promoters in various human cancers [ 6 – 9 ]. Moreover, emerging reports confirmed that miR-98-5p was downregulated and correlated with malignant progression in certain carcinoma, including HCC, ovarian cancer, colon cancer and lung cancer [ 10 – 13 ]. However, the role of miR-98-5p in PDAC remained to be elucidated.…”

Section: Introductionmentioning

confidence: 97%

Downregulated miR-98-5p promotes PDAC proliferation and metastasis by reversely regulating MAP4K4

Liu

Chen

et al. 2018

J Exp Clin Cancer Res

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BackgroundThe aberrant expression of microRNAs (miRNAs) has emerged as important hallmarks of cancer. However, the molecular mechanisms underlying the differences of miRNA expression remain unclear. Many studies have reported that miR-98-5p plays vital functions in the development and progression of multiple cancers. However, its role in pancreatic ductal adenocarcinoma (PDAC) remains unknown.MethodsThe expression of miR-98-5p and its specific target gene were determined in human PDAC specimens and cell lines by miRNA qRT-PCR, qRT-PCR and western blot. The effects of miR-98-5p depletion or ectopic expression on PDAC proliferation, migration and invasion were evaluated in vitro using CCK-8 proliferation assays, colony formation assays, wound healing assays and transwell assays. Furthermore, the in vivo effects were investigated using the mouse subcutaneous xenotransplantation and pancreatic tail xenotransplantation models. Luciferase reporter assays were employed to identify interactions between miR-98-5p and its specific target gene.ResultsMiR-98-5p expression was significantly lower in cancerous tissues and associated with tumor size, TNM stage, lymph node metastasis and survival. Notably, a series of gain- and loss-of-function assays elucidated that miR-98-5p suppressed PDAC cell proliferation, migration and invasion both in vitro and in vivo. Luciferase reporter assays, western blot and qRT-PCR revealed MAP4K4 to be a direct target of miR-98-5p. The effects of ectopic miR-98-5p were rescued by MAP4K4 overexpression. In contrast, the effects of miR-98-5p depletion were impaired by MAP4K4 knockdown. Furthermore, miR-98-5p suppressed the MAPK/ERK signaling pathway through downregulation of MAP4K4. In addition, the expression level of miR-98-5p was negatively correlated with MAP4K4 expression in PDAC tissues and cell lines.ConclusionsThese results suggest that downregulation of miR-98-5p promotes tumor development by downregulation of MAP4K4 and inhibition of the downstream MAPK/ERK signaling, thus, highlighting the potential of miR-98-5p as a therapeutic target for PDAC.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0807-2) contains supplementary material, which is available to authorized users.

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“…miR-98-5p, a member of the let-7 family of miRNAs, is associated with a number of types of cancer, including lung cancer, colorectal cancer and breast cancer ( 18 - 21 ). It has been reported that miR-98-5p enhances radiosensitivity and chemosensitivity, while it inhibits proliferation, migration and invasion in NSCLC ( 22 - 24 ). However, the inherent molecular mechanisms through which miR-98-5p affects NSCLC progression remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-98-5p inhibits proliferation and metastasis in non-small cell lung cancer by targeting TGFBR1

Jiang¹,

Yu²,

Chu³

et al. 2018

Int J Oncol

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MicroRNAs (miRNAs or miRs) have recently emerged as key regulators of various types of cancer, including non-small cell lung cancer (NSCLC). The disrupted expression of miRNAs is associated with tumorigenesis and metastasis; however, the underlying mechanisms remain unclear. In this study, we demonstrate that miR-98-5p is downregulated in NSCLC and that miR-98-5p deficiency is associated with an advanced clinical stage and metastasis. A dual-luciferase reporter assay was performed to confirm that transforming growth factor beta receptor 1 (TGFBR1), a key stimulator of tumor proliferation and metastasis, was a direct target of miR-98-5p. miR-98-5p overexpression resulted in the downregulation of TGFBR1 and the suppression of the viability, proliferation, migration and invasion of A549 and H1299 cells. Furthermore, miR-98-5p was demonstrated to be an efficient suppressor of tumor growth in an A549 subcutaneous xenograft tumor mouse model. Finally, miR-98-5p overexpression exerted a significant anti-metastatic effect in a mouse model of pulmonary metastasis. On the whole, the results of the present study suggest that miR-98-5p/TGFBR1 may serve as promising targets for NSCLC therapy.

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miR-98 inhibits expression of TWIST to prevent progression of non-small cell lung cancers

Cited by 26 publications

References 31 publications

A Plasma Biomarker Panel of Four MicroRNAs for the Diagnosis of Prostate Cancer

A Plasma Biomarker Panel of Four MicroRNAs for the Diagnosis of Prostate Cancer

Downregulated miR-98-5p promotes PDAC proliferation and metastasis by reversely regulating MAP4K4

MicroRNA-98-5p inhibits proliferation and metastasis in non-small cell lung cancer by targeting TGFBR1

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