MiR-138-5p Suppresses Cell Growth and Migration in Melanoma by Targeting Telomerase Reverse Transcriptase

Recent evidence suggests the existence of a miRNA regulatory network involving human telomerase reverse transcriptase gene (hTERT), with miR-138-5p playing a central role in many types of cancers. However, little is known about the regulation of hTERT expression by microRNA (miRNAs) in melanocytic tumors. Here, we investigated the effects of miR-138-5p in hTERT regulation in melanoma cells lines. In vitro studies demonstrated higher miR-138-5p and lower hTERT messenger RNA (mRNA) expression in human epidermal melanocytes, compared with melanoma cell lines (A2058, A375, SK-MEL-28) by quantitative polymerase chain reaction (qPCR) observing a negative correlation between them. A2058 melanoma cells were selected to be transfected with miR-138-5p mimic or inhibitor. Using luciferase assay, hTERT was identified as a direct target of this miRNA. Overexpression of miR-138-5p detected by Western blot revealed a decrease in hTERT protein expression (p = 0.012), and qPCR showed a reduction in telomerase activity (p < 0.001). Moreover, suppressions in cell growth (p = 0.035) and migration abilities (p = 0.015) were observed in A2058-transfected cells using thiazolyl blue tetrazolium bromide and flow cytometry, respectively. This study identifies miR-138-5p as a crucial tumor suppressor miRNA involved in telomerase regulation. Targeting it as a combination therapy with immunotherapy or targeted therapies could be used in advanced melanoma treatment; however, more preclinical studies are necessary.

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Inhibition of the Motility and Growth of B16F10 Mouse Melanoma Cells by Dominant Negative Mutants of Dok-1

Molecular and Cellular Biology ◽

10.1128/mcb.21.16.5437-5446.2001 ◽

2001 ◽

Vol 21 (16) ◽

pp. 5437-5446 ◽

Cited By ~ 20

Author(s):

Tetsuya Hosooka ◽

Tetsuya Noguchi ◽

Hiroshi Nagai ◽

Tatsuya Horikawa ◽

Takashi Matozaki ◽

...

Keyword(s):

Cell Growth ◽

Tyrosine Kinases ◽

Cell Spreading ◽

Melanoma Cells ◽

Dominant Negative ◽

Pleckstrin Homology Domain ◽

Pleckstrin Homology ◽

Cell Growth And Migration ◽

Mouse Melanoma ◽

And Migration

ABSTRACT Dok-1 (p62Dok) is a multiple-site docking protein that acts downstream of receptor and nonreceptor tyrosine kinases. Although it has been proposed to contribute to the control of cell growth and migration through association with the Ras GTPase-activating protein and the adapter protein Nck, the role of Dok-1 remains largely unknown. The functions of Dok-1 have now been investigated by the generation of two different COOH-terminal truncation mutants of this protein: one (DokPH+PTB) containing the pleckstrin homology and phosphotyrosine-binding domains, and the other (DokPH) composed only of the pleckstrin homology domain. Both of these mutant proteins were shown to act in a dominant negative manner. Overexpression of each of the mutants in highly metastatic B16F10 mouse melanoma cells thus both inhibited the tyrosine phosphorylation of endogenous Dok-1 induced by cell adhesion as well as reduced the association of the endogenous protein with cellular membranes and the cytoskeleton. Overexpression of DokPH+PTB in these cells also markedly reduced both the rates of cell spreading, migration, and growth as well as the extent of Ras activation. The effects of DokPH on these processes were less pronounced than were those of DokPH+PTB, indicating the importance of the phosphotyrosine-binding domain. These results suggest that at least in B16F10 cells, Dok-1 positively regulates not only cell spreading and migration but also cell growth and Ras activity.

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miR-338-5p inhibits cell growth and migration via inhibition of the METTL3/m6A/c-Myc pathway in lung cancer

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmaa170 ◽

2020 ◽

Author(s):

Hongyu Wu ◽

Fangjuan Li ◽

Ren Zhu

Keyword(s):

Lung Cancer ◽

Cell Growth ◽

Cancer Cells ◽

Quantitative Polymerase Chain Reaction ◽

Lung Cancer Cells ◽

Cell Counting ◽

Luciferase Reporter ◽

Cell Growth And Migration ◽

Public Health Burden ◽

And Migration

Abstract Lung cancer is a common type of cancer that causes a very large public health burden worldwide. Achieving a better understanding of the molecular mechanism underlying the progression of lung cancer is of benefit for the diagnosis, prognosis, and treatment of lung cancer. Here, we first identified dramatically decreased expression of miR-338-5p in lung cancer tissues and cells using quantitative polymerase chain reaction (qPCR) analysis. We then revealed that miR-338-5p inhibited the cell growth and migration of lung cancer cells using cell counting kit 8 (CCK8), EdU, and Transwell analysis. Furthermore, we demonstrated that miR-338-5p inhibited METTL3 expression by qPCR, western blot analysis, and luciferase reporter assay, while upregulation of METTL3 alleviated the role of miR-338-5p in lung cancer cells. We also showed that METTL3 promoted c-Myc expression by increasing the m6A modification of c-Myc, and overexpression of c-Myc restored the inhibition of cell growth and migration of lung cancer cells induced by METTL3 silencing. Ultimately, this research illustrated that modification of the miR-338-5p/METTL3/c-Myc pathway affected cellular progression in lung cancer cells. Collectively, our study revealed the underlying mechanism of miR-338-5p in lung cancer, providing a novel regulatory pathway in lung cancer. There is potential for this pathway to serve as a diagnostic, prognostic, and therapeutic biomarker for lung cancer.

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Effects of inhibition of hedgehog signaling on cell growth and migration of uveal melanoma cells

Cancer Biology & Therapy ◽

10.4161/cbt.28157 ◽

2014 ◽

Vol 15 (5) ◽

pp. 544-559 ◽

Cited By ~ 10

Author(s):

Fei Duan ◽

Ming Lin ◽

Chuanyin Li ◽

Xia Ding ◽

Guanxiang Qian ◽

...

Keyword(s):

Cell Growth ◽

Uveal Melanoma ◽

Hedgehog Signaling ◽

Melanoma Cells ◽

Cell Growth And Migration ◽

And Migration

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Knockout of Ajuba Attenuates the Growth and Migration of Hepatocellular Carcinoma Cells

Cytogenetic and Genome Research ◽

10.1159/000512264 ◽

2020 ◽

Vol 160 (11-12) ◽

pp. 650-658

Author(s):

Yichen Le ◽

Yi He ◽

Meirong Bai ◽

Ying Wang ◽

Jiaxue Wu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Growth ◽

Cancer Progression ◽

Normal Liver ◽

Cell Growth And Migration ◽

And Migration ◽

Hcc Cells

Ajuba has been found to be mutated or aberrantly regulated in several human cancers and plays important roles in cancer progression via different signaling pathways. However, little is known about the role of Ajuba in hepatocellular carcinoma (HCC). Here, we found an upregulation of Ajuba expression in HCC tissues compared with normal liver tissues, while a poor prognosis was observed in HCC patients with high Ajuba expression. Knockout of Ajuba in HCC cells inhibited cell growth in vitro and in vivo, suppressed cell migration, and enhanced the cell apoptosis under stress. Moreover, re-expression of Ajuba in Ajuba-deficient cells could restore the phenotype of Ajuba-deficient cells. In conclusion, these results indicate that Ajuba is upregulated in HCC and promotes cell growth and migration of HCC cells, suggesting that Ajuba could possibly be a new target for HCC diagnosis and treatment.

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LINC01234 aggravates cell growth and migration of triple‐negative breast cancer by activating the Wnt pathway

Environmental Toxicology ◽

10.1002/tox.23318 ◽

2021 ◽

Author(s):

Feng Xiao ◽

Hongyao Jia ◽

Di Wu ◽

Zhiru Zhang ◽

Sijie Li ◽

...

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Triple Negative Breast Cancer ◽

Wnt Pathway ◽

Triple Negative ◽

Cell Growth And Migration ◽

And Migration

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Development of a Decellularized Porcine Esophageal Matrix for Potential Applications in Cancer Modeling

Cells ◽

10.3390/cells10051055 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1055

Author(s):

Hersh Chaitin ◽

Michael L. Lu ◽

Michael B. Wallace ◽

Yunqing Kang

Keyword(s):

Cell Growth ◽

Lymphatic Vessels ◽

Significant Loss ◽

Cancer Cell Growth ◽

Cell Growth And Migration ◽

Decellularized Extracellular Matrix ◽

Cancer Models ◽

The Matrix ◽

Potential Applications ◽

And Migration

Many decellularized extracellular matrix-derived whole organs have been widely used in studies of tissue engineering and cancer models. However, decellularizing porcine esophagus to obtain decellularized esophageal matrix (DEM) for potential biomedical applications has not been widely investigated. In this study a modified decellularization protocol was employed to prepare a porcine esophageal DEM for the study of cancer cell growth. The cellular removal and retention of matrix components in the porcine DEM were fully characterized. The microstructure of the DEM was observed using scanning electronic microscopy. Human esophageal squamous cell carcinoma (ESCC) and human primary esophageal fibroblast cells (FBCs) were seeded in the DEM to observe their growth. Results show that the decellularization process did not cause significant loss of mechanical properties and that blood ducts and lymphatic vessels in the submucosa layer were also preserved. ESCC and FBCs grew on the DEM well and the matrix did not show any toxicity to cells. When FBS and ESCC were cocultured on the matrix, they secreted more periostin, a protein that supports cell adhesion on matrix. This study shows that the modified decellularization protocol can effectively remove the cell materials and maintain the microstructure of the porcine esophageal matrix, which has the potential application of studying cell growth and migration for esophageal cancer models.

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