Tumor-suppressive function of <i>UNC5D</i> in papillary thyroid cancer

Zhang, Manman; Sun, Feng; Cui, Bing; Zhang, Lele; Fang, Yun; Li, Yan; Zhang, Ruijia; Ye, Xiaoping; Ma, Yuru; Han, Bing; Song, Hwangjun

doi:10.18632/oncotarget.21759

Cited by 9 publications

(5 citation statements)

References 41 publications

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“…Human PTC K1 cells were used in the present study. Though we lately discovered K1 cells were actually cells mixed with GLAG-66 cells, of the thyroid gland papillary carcinoma, it did not affect studying function of the target gene on PTC, which was verified by numerous researches before ( 21 – 30 ). K1 cells (mixed thyroid gland papillary carcinoma cells) were purchased from ATCC (Guangzhou, China) were cultured in Dulbecco's modified Eagle's medium (DMEM) of 10% fetal bovine serum (FBS; both Gibco; Thermo Fisher Scientific, Inc., Waltham, MA, USA) and 1% penicillin/streptomycin (Invitrogen, Carlsbad, CA, USA) at 37°C with 5% CO 2.…”

Section: Methodsmentioning

confidence: 81%

Telomerase reverse transcriptase induced thyroid carcinoma cell proliferation through PTEN/AKT signaling pathway

Zhang

2018

Mol Med Report

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Thyroid carcinoma is the most common endocrine malignant tumor in the world, and so, there is a requirement to develop novel molecular targets for thyroid cancer diagnosis and treatment. Telomerase reverse transcriptase (TERT) was revealed to promote cell proliferation in a number of types of cell. To evaluate whether and how TERT functioned on papillary thyroid cancer (PTC) cell proliferation, the present study constructed TERT over-expression [recombined (r)TERT plasmid group] and interference [small interfering RNA (si)-TERT group] models by liposome transfection respectively to study the molecular mechanisms. The transfection efficiency was first detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting to analyze TERT levels compared with the negative control (NC) and control groups. Then MTT and carboxyfluorescein diacetate succinimidyl ester assays were performed to determine living cell proliferation and total cell proliferation respectively. Propidium iodide assay was used to detect alterations in cell cycle progression. RT-qPCR and western blotting were performed to detect associated factor variation. The results demonstrated that, following the generation of TERT overexpression or silencing PTC cells, the living cells and also total cell proliferation increased significantly in the rTERT group, and decreased significantly in siTERT group, when compared with the NC and control groups. The cell cycle was accelerated in the rTERT group, and blocked in the G1/S transition in the siTERT group. The mRNA and protein levels of P27, P53 and phosphatase and tensin homolog (PTEN) decreased significantly in the rTERP group and increased in the siTERP group, while cyclin dependent kinase 2 and Cyclin D1 increased significantly in the rTERP group and decreased in the siTERP group. The expression of cell division cycle 25A did not alter significantly. The protein levels of β-catenin and retinoblastoma were also unaltered. Protein kinase B (AKT) was detected once activated by TERT, and there were increased phosphorylated (p)-AKT protein levels in the rTERT group, and decreased p-AKT protein levels in the siTERT group. In conclusion, TERT could induce thyroid carcinoma cell proliferation mainly through the PTEN/AKT signaling pathway.

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Section: Methodsmentioning

confidence: 81%

Telomerase reverse transcriptase induced thyroid carcinoma cell proliferation through PTEN/AKT signaling pathway

Zhang

2018

Mol Med Report

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“…UNC5D, as a member of the UNC5 family, was identified as a netrin receptor and participated in cell migration and morphogenesis during development [ 27 ]. Previously, UNC5D was found to be a tumor suppressor and frequently downregulated in primary renal cell carcinomas [ 18 ], neuroblastoma [ 28 , 29 ], bladder cancer [ 30 ] and papillary thyroid cancer [ 31 ]. Recently, Dong D et al found UNC5D as a putative metastatic suppressor gene that is commonly downregulated by hypermethylation in PCa [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Exome sequencing identifies somatic mutations in novel driver genes in non-small cell lung cancer

Zhang

et al. 2020

Aging

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Lung cancer is the leading cause of cancer death worldwide and accounts for more than one-third of all newly diagnosed cancer cases in China. Therefore, it is of great clinical significance to explore new driver gene mutations in non-small-cell lung cancer (NSCLC). Using an initial bioinformatic analysis, we identified somatic gene mutations in 13 patients with NSCLC and confirmed these mutations by targeted sequencing in an extended validation group of 88 patients. Recurrent mutations were detected in UNC5D (7.9%), PREX1 (5.0%), HECW1 (4.0%), DACH1 (2.0%), and GPC5 (2.0%). A functional study was also performed in UNC5D mutants. Mutations in UNC5D promoted tumorigenesis by abolishing the tumor suppressor function of the encoded protein. Additionally, in ten patients with lung squamous cell carcinoma, we identified mutations in KEAP1/NFE2L2 that influenced the expression of target genes in vivo and in vitro . Overall, the results of our study expanded the known spectrum of driver mutations involved in the pathogenesis of NSCLC.

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“…On the other hand, Adam23 has been demonstrated to suppress cancer cell metastasis through the interaction with integrins [ 26 ]. Furthermore, such tumor suppressor role has also been demonstrated for Unc5d [ 27 ]. Again, these effects were also supported by the pathway analysis linking miRNA-26b for example to pancreatic cancer and proteoglycans and other cancer related pathways.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome signature of miRNA-26b KO mouse model suggests novel targets

Vorst¹,

Pepe

Peters³

et al. 2021

BMC Genom Data

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Background MicroRNAs (miRNAs) are short (20–24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. One of the miRNAs that has been shown to play a role in various pathologies like cancer, neurological disorders and cardiovascular diseases is miRNA-26b. However, these studies only demonstrated rather ambiguous associations without revealing a causal relationship. Therefore, the aim of this study is to establish and validate a mouse model which enables the elucidation of the exact role of miRNA-26b in various pathologies. Results A miRNA-26b-deficient mouse model was established using homologous recombination and validated using PCR. miRNA-26b-deficient mice did not show any physiological abnormalities and no effects on systemic lipid levels, blood parameters or tissue leukocytes. Using next generation sequencing, the gene expression patterns in miRNA-26b-deficient mice were analyzed and compared to wild type controls. This supported the already suggested role of miRNA-26b in cancer and neurological processes, but also revealed novel associations of miRNA-26b with thermogenesis and allergic reactions. In addition, detailed analysis identified several genes that seem to be highly regulated by miRNA-26b, which are linked to the same pathological conditions, further confirming the role of miRNA-26b in these pathologies and providing a strong validation of our mouse model. Conclusions miRNA-26b plays an important role in various pathologies, although causal relationships still have to be established. The described mouse model of miRNA-26b deficiency is a crucial first step towards the identification of the exact role of miRNA-26b in various diseases that could identify miRNA-26b as a promising novel diagnostic or even therapeutic target in a broad range of pathologies.

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Tumor-suppressive function of UNC5D in papillary thyroid cancer

Cited by 9 publications

References 41 publications

Telomerase reverse transcriptase induced thyroid carcinoma cell proliferation through PTEN/AKT signaling pathway

Telomerase reverse transcriptase induced thyroid carcinoma cell proliferation through PTEN/AKT signaling pathway

Exome sequencing identifies somatic mutations in novel driver genes in non-small cell lung cancer

Transcriptome signature of miRNA-26b KO mouse model suggests novel targets

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