Dataset Information

CITED1 promotes proliferation of papillary thyroid cancer cells via the regulation of p21 and p27.

ABSTRACT:

Background

It has been reported that CBP/p300-Interacting Transactivator with glutamic acid [E]/aspartic acid [D]-rich C-terminal domain 1 (CITED1) is overexpressed in papillary thyroid cancer (PTC). However, the functional significance and underlying mechanisms of CITED1 in PTC are largely unknown.

Methods

The Cancer Genome Atlas dataset and real-time PCR were used to determine the expression of CITED1 in PTC. The role of CITED1 in PTC cell proliferation was determined conducted using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, and flow cytometry assays in vitro, and a subcutaneous xenotransplantation tumor model in nude mice was established to analyze tumor growth in vivo. We studied the potential mechanisms underlying the contribution of CITED1 to PTC proliferation using western blotting and luciferase assays.

Results

We found that CITED1 was highly expressed in PTC. In vitro and in vivo experiments demonstrated that CITED1 was involved in PTC cell proliferation and tumorigenesis. Then, gain- and loss-of-function experiments revealed that CITED1 decreased the expression of p21 and p27, and thereby increased the phosphorylation of pRb as well as E2F1 transcriptional activity.

Conclusions

Our results suggest that CITED1 is overexpressed in PTC and that CITED1 promotes the proliferation of PTC cells via the regulation of p21 and p27, which indicates that CITED1 might be a potential therapeutic target in the treatment of PTC.

SUBMITTER: Li H

PROVIDER: S-EPMC6219258 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

CITED1 promotes proliferation of papillary thyroid cancer cells via the regulation of p21 and p27.

Li Hai H Guan Hongyu H Guo Yan Y Liang Weiwei W Liu Liehua L He Xiaoying X Ke Weijian W Cao Xiaopei X Xiao Haipeng H Li Yanbing Y

Cell & bioscience 20181106

<h4>Background</h4>It has been reported that CBP/p300-Interacting Transactivator with glutamic acid [E]/aspartic acid [D]-rich C-terminal domain 1 (CITED1) is overexpressed in papillary thyroid cancer (PTC). However, the functional significance and underlying mechanisms of CITED1 in PTC are largely unknown.<h4>Methods</h4>The Cancer Genome Atlas dataset and real-time PCR were used to determine the expression of CITED1 in PTC. The role of CITED1 in PTC cell proliferation was determined conducted ...[more]

PMID: 30450190

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Project description:Background Based on existing evidence, microRNAs (miRs) are gene regulators that undertake key functions in the oncogenesis and tumor progression of every single human malignant disease, such as thyroid carcinoma (TC). Previous clinical findings showed that expression of miR-195 is down-regulated in TC, which implies that miR-195 may be practically involved in TC pathogenesis. Nevertheless, the function of hsa-miR-195-5p in TC is still largely unclear. Herein, we detected the conceivable involvement of hsa-miR-195-5p in TC cell proliferation. Methods Real time PCR examination was performed to assess the expression level of hsa-miR-195-5p in TC cell lines TPC-1 and B-CPAP. TPC-1 cells were transfected with either hsa-miR-195-5p mimics or hsa-miR-195-5p inhibitor. After confirmation of transfection efficiency, the effect of hsa-miR-195-5p on proliferation and cell cycle of TPC-1 cells was assessed. The expression of cyclin D1 and p21 was simultaneously detected by western blotting. Moreover, targetScan 6.2 was used to predict hsa-miR-195-5p target genes. Subsequently, luciferase reporter was performed to examine whether there is a possible binding of hsa-miR-195-5p to 3’-UTR of cyclin D1 mRNA. Furthermore, cyclin D1 mRNA and protein levels were measured to check whether hsa-miR-195-5p exerts its function at the post-transcriptional level. In addition, to explore the function of cyclin D1 in TPC-1 cells overexpressing hsa-miR-195-5p, cyclin D1 siRNA was used to silence the expression of cyclin D1 in TPC-1 cells overexpressing hsa-miR-195-5p. Results We quantified the expression of hsa-miR-195-5p in TC cells and normal thyroid cells and found a remarkable decrease in hsa-miR-195-5p expression in TC cells. Over-expression of hsa-miR-195-5p obviously resulted in downgraded proliferation of TC cells. Moreover, hsa-miR-195-5p caused cell arrest at the GO/G1 phase. Further in silico analyses and the dual-luciferase reporter assay confirmed that 3’-UTR of cyclin D1 is a direct target of hsa-miR-195-5p. Western blot analysis uncovered that hsa-miR-195-5p over-expression led to decreased levels of cyclin D1 and p21. In mechanistic analyses, we found that silencing of cyclin D1 reversed the inhibitory effect of hsa-miR-195-5p on the proliferation of TC cells, which indicates that hsa-miR-195-5p suppresses TC cell proliferation by adversely regulating cyclin D1. Conclusions We concluded that hsa-miR-195-5p is a candidate tumor-suppressor miRNA in TC and that the hsa-miR-195-5p/p21/cyclin D1 pathway could be a potential therapeutic target for TC.

Dataset Information

CITED1 promotes proliferation of papillary thyroid cancer cells via the regulation of p21 and p27.

Background

Methods

Results

Conclusions

Publications

CITED1 promotes proliferation of papillary thyroid cancer cells via the regulation of p21 and p27.

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