TNRC6C Functions as a Tumor Suppressor and Is Frequently Downregulated in Papillary Thyroid Cancer

Our previous study found that trinucleotide repeat containing adaptor 6C (TNRC6C) may act as a tumor suppressor in papillary thyroid cancer (PTC). In this study, we aimed to confirm the effect of TNRC6C on PTC and investigate the underlying molecular mechanism. The difference of mRNA level of TNRC6C...

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Main Authors: Zhenqin Cai, Tianyu Zhai, Dilidaer Muhanhali, Yan Ling
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:International Journal of Endocrinology
Online Access:http://dx.doi.org/10.1155/2021/6686998
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author Zhenqin Cai
Tianyu Zhai
Dilidaer Muhanhali
Yan Ling
author_facet Zhenqin Cai
Tianyu Zhai
Dilidaer Muhanhali
Yan Ling
author_sort Zhenqin Cai
collection DOAJ
description Our previous study found that trinucleotide repeat containing adaptor 6C (TNRC6C) may act as a tumor suppressor in papillary thyroid cancer (PTC). In this study, we aimed to confirm the effect of TNRC6C on PTC and investigate the underlying molecular mechanism. The difference of mRNA level of TNRC6C between PTC tissue and noncancerous thyroid tissue and the association of expression level of TNRC6C with clinicopathological features of PTC were analyzed using TCGA data. Immunohistochemical assay was performed to detect the protein expression of TNRC6C in PTC and its adjacent noncancerous tissue. Cell proliferation, migration, invasion, and apoptosis were analyzed after knockdown or overexpression of TNRC6C in BCPAP cells. RNA-sequencing was performed to find the target genes of TNRC6C, and potential targets were validated in BCPAP and TPC1 cells. Our results showed that TNRC6C was downregulated in PTC, and lower expression level of TNRC6C was associated with worse clinicopathological features. Overexpression of TNRC6C significantly inhibited proliferation, migration, and invasion of BCPAP cells and promoted its apoptosis, while knockdown of TNRC6C acted the opposite role. By analyzing RNA-sequencing data and TCGA data, 12 genes (SCD, CRLF1, APCDD1L, CTHRC1, PTPRU, ALDH1A3, VCAN, TNC, ECE1, COL1A1, CAMK2N2, and MMP14) were considered as potential target genes of TNRC6C, and most of them were associated with clinicopathological features of PTC in TCGA. All of them except CAMK2N2 were significantly downregulated after overexpressing TNRC6C. Our study demonstrated that TNRC6C functions as a tumor suppressor in PTC and may serve as a useful therapeutic target and prognostic marker for PTC patients.
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spelling doaj-art-84f6d85d7adc4af09da32abff5bf03ce2025-02-03T05:49:15ZengWileyInternational Journal of Endocrinology1687-83371687-83452021-01-01202110.1155/2021/66869986686998TNRC6C Functions as a Tumor Suppressor and Is Frequently Downregulated in Papillary Thyroid CancerZhenqin Cai0Tianyu Zhai1Dilidaer Muhanhali2Yan Ling3Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai 200032, ChinaDepartment of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai 200032, ChinaDepartment of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai 200032, ChinaDepartment of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai 200032, ChinaOur previous study found that trinucleotide repeat containing adaptor 6C (TNRC6C) may act as a tumor suppressor in papillary thyroid cancer (PTC). In this study, we aimed to confirm the effect of TNRC6C on PTC and investigate the underlying molecular mechanism. The difference of mRNA level of TNRC6C between PTC tissue and noncancerous thyroid tissue and the association of expression level of TNRC6C with clinicopathological features of PTC were analyzed using TCGA data. Immunohistochemical assay was performed to detect the protein expression of TNRC6C in PTC and its adjacent noncancerous tissue. Cell proliferation, migration, invasion, and apoptosis were analyzed after knockdown or overexpression of TNRC6C in BCPAP cells. RNA-sequencing was performed to find the target genes of TNRC6C, and potential targets were validated in BCPAP and TPC1 cells. Our results showed that TNRC6C was downregulated in PTC, and lower expression level of TNRC6C was associated with worse clinicopathological features. Overexpression of TNRC6C significantly inhibited proliferation, migration, and invasion of BCPAP cells and promoted its apoptosis, while knockdown of TNRC6C acted the opposite role. By analyzing RNA-sequencing data and TCGA data, 12 genes (SCD, CRLF1, APCDD1L, CTHRC1, PTPRU, ALDH1A3, VCAN, TNC, ECE1, COL1A1, CAMK2N2, and MMP14) were considered as potential target genes of TNRC6C, and most of them were associated with clinicopathological features of PTC in TCGA. All of them except CAMK2N2 were significantly downregulated after overexpressing TNRC6C. Our study demonstrated that TNRC6C functions as a tumor suppressor in PTC and may serve as a useful therapeutic target and prognostic marker for PTC patients.http://dx.doi.org/10.1155/2021/6686998
spellingShingle Zhenqin Cai
Tianyu Zhai
Dilidaer Muhanhali
Yan Ling
TNRC6C Functions as a Tumor Suppressor and Is Frequently Downregulated in Papillary Thyroid Cancer
International Journal of Endocrinology
title TNRC6C Functions as a Tumor Suppressor and Is Frequently Downregulated in Papillary Thyroid Cancer
title_full TNRC6C Functions as a Tumor Suppressor and Is Frequently Downregulated in Papillary Thyroid Cancer
title_fullStr TNRC6C Functions as a Tumor Suppressor and Is Frequently Downregulated in Papillary Thyroid Cancer
title_full_unstemmed TNRC6C Functions as a Tumor Suppressor and Is Frequently Downregulated in Papillary Thyroid Cancer
title_short TNRC6C Functions as a Tumor Suppressor and Is Frequently Downregulated in Papillary Thyroid Cancer
title_sort tnrc6c functions as a tumor suppressor and is frequently downregulated in papillary thyroid cancer
url http://dx.doi.org/10.1155/2021/6686998
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AT dilidaermuhanhali tnrc6cfunctionsasatumorsuppressorandisfrequentlydownregulatedinpapillarythyroidcancer
AT yanling tnrc6cfunctionsasatumorsuppressorandisfrequentlydownregulatedinpapillarythyroidcancer