MicroRNA-365 inhibits growth, invasion and metastasis of malignant melanoma by targeting NRP1 expression

Bai, Juanjuan; Zhang, Zhongling; Li, Xing; Liu, Huifan

doi:10.3233/cbm-150500

Cited by 51 publications

(48 citation statements)

References 29 publications

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“…These data indicate that NRP1 may act as a downstream effector in the miR-9-mediated malignant phenotypes of MM cells. In addition, miR-365 was also found to inhibit the growth, invasion, and metastasis of MM by targeting NRP1 expression 32. Therefore, our study expands the importance of the miRs/NRP1 axis in MM.…”

Section: Discussionsupporting

confidence: 64%

MicroRNA-9 suppresses the growth, migration, and invasion of malignant melanoma cells via targeting NRP1

Xu¹,

Chen²,

He³

et al. 2016

OTT

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MicroRNAs (miRs) are a class of small noncoding RNAs that negatively regulate the gene expression by directly binding to the 3′ untranslated region of their target mRNA, thus resulting in mRNA degradation or translational repression. miR-9 has recently been demonstrated to play a role in the development and progression of malignant melanoma (MM), but the regulatory mechanism of miR-9 in the malignant phenotypes of MM still remains largely unknown. In this study, a total of 73 pairs of MM tissues and adjacent normal tissues were collected. Real-time reverse transcription polymerase chain reaction and Western blot were used to detect the mRNA and protein expression of miR-9. MTT assay, wound healing assay, and transwell assay were conducted to determine the cell proliferation, migration, and invasion. Luciferase reporter assay was used to determine the targeting relationship between miR-9 and NRP1. Our data demonstrated that miR-9 expression was significantly downregulated in MM tissues compared with that in adjacent normal tissues. The decreased miR-9 level was significantly associated with the tumor stage and metastasis of MM. We also found that the expression level of miR-9 was decreased in MM cell lines (G361, B16, A375, and HME1) compared with normal skin HACAT cells. Ectopic expression of miR-9 led to a significant decrease in the ability of proliferation, migration, and invasion in A375 cells. NRP1 was further identified as a direct target gene of miR-9, and the protein expression of NRP1 was negatively regulated by miR-9 in A375 cells. Furthermore, overexpression of NRP1 reversed the suppressive effects of miR-9 on the malignant phenotypes of A375 cells. In vivo study revealed that miR-9 overexpression decreased the tumor growth, while overexpression of NRP1 increased MM growth. In summary, our findings suggest that the miR-9/NRP1 axis may serve as a potential target for the treatment of MM.

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Section: Discussionsupporting

confidence: 64%

MicroRNA-9 suppresses the growth, migration, and invasion of malignant melanoma cells via targeting NRP1

Xu¹,

Chen²,

He³

et al. 2016

OTT

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“…1), also encodes an miRNA with known tumour suppressor function, as evidenced by its ability to target specific transcription factors, such as NKX2-1 and TTF1, in non-small cell lung cancer (Qi et al 2012; Kang et al 2013; Sun et al 2015). miR365 is down-regulated in colon cancer (Nie et al 2012), cutaneous squamous cell carcinoma (Zhou et al 2014, 2015), hepatocellular carcinoma (Chen et al 2015), gastric cancer (Guo et al 2013) and malignant melanoma (Bai et al 2015a, b). By contrast, putative tumour suppressor functions of the other two miRNAs located within the NF1 microdeletion region, encoded by MIR4725 and MIR4733, respectively, have not so far been reported.…”

Section: Co-deleted Genes With the Potential To Influence The Clinicamentioning

confidence: 99%

Emerging genotype–phenotype relationships in patients with large NF1 deletions

2017

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The most frequent recurring mutations in neurofibromatosis type 1 (NF1) are large deletions encompassing the NF1 gene and its flanking regions (NF1 microdeletions). The majority of these deletions encompass 1.4-Mb and are associated with the loss of 14 protein-coding genes and four microRNA genes. Patients with germline type-1 NF1 microdeletions frequently exhibit dysmorphic facial features, overgrowth/tall-for-age stature, significant delay in cognitive development, large hands and feet, hyperflexibility of joints and muscular hypotonia. Such patients also display significantly more cardiovascular anomalies as compared with patients without large deletions and often exhibit increased numbers of subcutaneous, plexiform and spinal neurofibromas as compared with the general NF1 population. Further, an extremely high burden of internal neurofibromas, characterised by >3000 ml tumour volume, is encountered significantly, more frequently, in non-mosaic NF1 microdeletion patients than in NF1 patients lacking such deletions. NF1 microdeletion patients also have an increased risk of malignant peripheral nerve sheath tumours (MPNSTs); their lifetime MPNST risk is 16–26%, rather higher than that of NF1 patients with intragenic NF1 mutations (8–13%). NF1 microdeletion patients, therefore, represent a high-risk group for the development of MPNSTs, tumours which are very aggressive and difficult to treat. Co-deletion of the SUZ12 gene in addition to NF1 further increases the MPNST risk in NF1 microdeletion patients. Here, we summarise current knowledge about genotype–phenotype relationships in NF1 microdeletion patients and discuss the potential role of the genes located within the NF1 microdeletion interval whose haploinsufficiency may contribute to the more severe clinical phenotype.

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“…Therefore, it is urgently needed to develop novel specific biomarkers for its early diagnosis and treatment. Recently, many oncogenes and tumor suppressor genes have been proved to be deregulated in melanoma, which contribute to its malignant progression [4–8]. …”

Section: Introductionmentioning

confidence: 99%

RAB22A overexpression promotes the tumor growth of melanoma

Chen

Zhu

et al. 2016

Oncotarget

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Malignant melanoma is the most aggressive type of skin cancer. RAB22A, a member of RAS oncogene family, has been found to be significantly upregulated in multiple human cancers. In the present study, we found that RAB22A mRNA expression was significantly upregulated in melanoma tissues (including 60 primary melanomas and 84 metastatic melanomas) compared to benign nevi (n = 20), which were significantly higher in metastatic melanoma tissues than primary tissues. Immunohistochemistry data further showed that the positive immunoreactivity of RAB22A was detected in 66% (95/144) melanoma tissues, but not in benign nevi. Moreover, high expression of RAB22A was significantly associated with advanced clinical stage in melanoma. Furthermore, patients with high RAB22A expression had shorter overall survival compared those with low expression of RAB22A. In-vitro study showed that RAB22A was also upregulated in melanoma cell lines WM35, A375, WM451, and SK-MEL-1, when compared with the normal melanocyte HM cells. Knockdown of RAB22A significantly reduced the proliferation, migration and invasion of melanoma A375 cells, while overexpression of RAB22A significantly promoted these malignant phenotypes. In addition, RAB22A was found to be a target of miR-203, a tumor suppressive miRNA in melanoma. Besides, miR-203 was downregulated in melanoma tissues and cell lines, when compared with benign nevi and HM cells, respectively. Taken these findings together, our study could validate an oncogenic role of RAB22A in melanoma, suggesting that RAB22A may be a potential therapeutic target for melanoma.

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MicroRNA-365 inhibits growth, invasion and metastasis of malignant melanoma by targeting NRP1 expression

Abstract: Our data suggest that miR-365 functions as a tumor suppressor in MM development and progression, and holds promise as a prognostic biomarker and potential therapeutic target for MM.

Cited by 51 publications

References 29 publications

MicroRNA-9 suppresses the growth, migration, and invasion of malignant melanoma cells via targeting NRP1

MicroRNA-9 suppresses the growth, migration, and invasion of malignant melanoma cells via targeting NRP1

Emerging genotype–phenotype relationships in patients with large NF1 deletions

RAB22A overexpression promotes the tumor growth of melanoma

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