Dataset Information

MiRNA-128-3p Restrains Malignant Melanoma Cell Malignancy by Targeting NTRK3.

ABSTRACT: The functions of non-coding RNA, including microRNA (miRNA), have attracted considerable attention in the field of oncology, In this report, we examined the roles and molecular mechanisms of miR-128-3p, as related to the biological behaviors of malignant melanoma (MM). We found that miR-128-3p was expressed in low levels in these MM cells and may serve as a tumor suppressor by inhibiting proliferation, migration, and invasion, as well as inducing apoptosis in these MM cells. Moreover, neurotrophin receptor 3 (NTRK3), which serves as an oncogene that can enhance malignant behaviors of MM cells, was up-regulated in MM cells. Our current survey disclosed a complementary binding between miR-128-3p and the NTRK3 3' untranslated regions (3'-UTR), while luciferase activities of NTRK3 3'-UTR were restrained by miR-128-3p in 293T cells. The effects of pre-miR-128-3p and sh-NTRK3 as well as anti-miR-128-3p and NTRK3(+) appeared to function synergistically in producing malignant progression. Moreover, there were possible to have counteracted effects for pre-miR-128-3p and NTRK3(+) in malignant progression. These findings established that miR-128-3p can function as a tumor suppressor by inhibiting carcinogenesis of the oncogene, NTRK3. Collectively, miR-128-3p and NTRK3 genes participate in modulating the malignant behavior of MM, and may represent new therapeutic targets for MM.

SUBMITTER: Zhou X

PROVIDER: S-EPMC7871904 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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MiRNA-128-3p Restrains Malignant Melanoma Cell Malignancy by Targeting NTRK3.

Zhou Xinxin X He Jiayuan J Wang Qingyuan Q Ma Teng T

Frontiers in oncology 20210126

The functions of non-coding RNA, including microRNA (miRNA), have attracted considerable attention in the field of oncology, In this report, we examined the roles and molecular mechanisms of miR-128-3p, as related to the biological behaviors of malignant melanoma (MM). We found that miR-128-3p was expressed in low levels in these MM cells and may serve as a tumor suppressor by inhibiting proliferation, migration, and invasion, as well as inducing apoptosis in these MM cells. Moreover, neurotroph ...[more]

PMID: 33575204

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Project description:Colorectal carcinoma (CRC) is a common malignant tumor of the digestive tract. It is characterized by a high degree of malignancy, early metastasis and poor prognosis. Studies have shown the effect of miR-369-3p on the biological function of a variety of tumors. However, the mechanism by which miR-369-3p and its potential target genes participate in the pathogenesis of CRC has not been elucidated. This study aims to study the relationship between miR-369-3p and transcription factor 4 (TCF4), to reveal the mechanism of the occurrence and development of CRC, and to provide a promising target for the treatment of CRC. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the miR-369-3p levels in CRC tissues and cells. miR-369-3p mimics and/or TCF4 overexpression vectors were transfected into SW480 cells. The expression of miR-369-3p and TCF4 mRNA was detected using RT-qPCR. Bioinformatics analysis predicted the binding site of miR-369-3p to the TCF4 3'UTR, and the targeting relationship was verified by a dual luciferase reporter gene assay. Cell proliferation and invasion were investigated by labeled immunofluorescence assay using BrdU antibody and Transwell assay. The oxidative stress ability of cells was determined by commercial kits. The levels of proteins related to cell proliferation and invasion were measured by western blotting. The level of miR-369-3p was significantly down-regulated in CRC tissues and cell lines, especially in SW480 cells (P<0.05). The expression of TCF4 was negatively correlated with that of miR-369-3p. High levels of miR-369-3p targeting TCF4 suppressed cell proliferation and downregulated the protein expression of Ki67 and PCNA (P<0.05). Overexpressed miR-369-3p binding TCF4 inhibited cell invasion and decreased the protein levels of vascular endothelial growth factor (VEGF) and E-cadherin (P<0.05). Furthermore, upregulation of miR-369-3p increased the activity of superoxide dismutase (SOD) while decreasing the content of malondialdehyde (MDA) and activity of lactate dehydrogenase (LDH) by blocking the expression of TCF4 (P<0.05). MiR-369-3p inhibits the proliferation, invasion and oxidative stress of CRC cells by targeting TCF4, thus defining miR-369-3p as a potential target for the diagnosis and treatment of CRC.

Project description:Temozolomide is a first line anti-tumor drug used for the treatment of patients with Glioblastoma multiforme (GBM). However, the drug resistance to temozolomide limits its clinical application. Therefore, novel strategies to overcome chemoresistance are desperately needed for improved treatment of human GBM. Recent studies have demonstrated that miRNAs are closely related to resistance to cancer chemotherapy. This study aimed to further validate the biological role of miR-128-3p and to investigate whether miR-128-3p can enhance the chemosensitivity of glioblastoma to temozolomide (TMZ) and the underlying mechanisms. The effects of miR-128-3p and TMZ on the proliferation of glioblastoma cells were investigated by cell counting kit-8 (cck8). Transwell and intracerebral invasion assays were applied to determine the effects of the combination of miR-128-3p and TMZ on the invasion and migration of glioblastoma in vitro and in vivo. Flow cytometry was used to detect apoptosis in each group, and immunofluorescence was used to determine the expression levels of EMT-related proteins. RT-PCR and Western-blot were applied to detect EMT-transformed proteins (c-Met, PDGFRα, Notch1, and Slug) and EMT phenotype-associated proteins (Vim, CD44, and E-cadherin) at both mRNA and protein levels. Based on the microRNA.org database, we predicted the target genes of miR-128-3p. The target-relationship between miR-128-3p and c-Met and PDGFRα was verified by dual luciferase reporter gene. The tumor volume, weight and the expression levels of the proteins described above were measured in subcutaneously transplanted tumor model in nude mice. We found that the expression of miR-128-3p was down-regulated in glioblastoma tissue samples and cell lines. miR-128-3p suppressed the proliferation, migration, and invasion of GBM both in vitro and in vivo; miR-128-3p enhanced the therapeutic effect of TMZ via inhibition of proliferation, invasion and migration of glioblastoma cells and induction of apoptosis. Overexpression of miR-128-3p down-regulated the expression levels of EMT-transformed proteins (c-Met, PDGFRα, Notch1 and Slug) to enhance the effect of TMZ. In addition, we found that miR-128-3p targeted and bound c-Met. More importantly, the upregulation of c-Met significantly prompted U87 and U251 cell proliferation. This effect could be abolished when c-Met was silenced. The investigation in tumor bearing nude mice showed that miR-128-3p in combination with TMZ reduced tumor volume and the invasion extent, and increased the sensitivity of glioblastoma to TMZ. miR-128-3p is capable of enhancing the sensitivity of glioblastoma to TMZ through regulating c-Met/EMT.

Dataset Information

MiRNA-128-3p Restrains Malignant Melanoma Cell Malignancy by Targeting NTRK3.

Publications

MiRNA-128-3p Restrains Malignant Melanoma Cell Malignancy by Targeting NTRK3.

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