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 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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SLC6A15 acts as a tumor suppressor to inhibit migration and invasion in human papillary thyroid cancer

Journal of Cellular Biochemistry ◽

10.1002/jcb.29914 ◽

2021 ◽

Author(s):

Yuxin Chen ◽

Hai Li ◽

Weiwei Liang ◽

Yan Guo ◽

Miaoguan Peng ◽

...

Keyword(s):

Thyroid Cancer ◽

Tumor Suppressor ◽

Papillary Thyroid Cancer ◽

Migration And Invasion ◽

Papillary Thyroid

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Long noncoding RNA FER1L4 promotes the malignant processes of papillary thyroid cancer by targeting the miR-612/ Cadherin 4 axis

Cancer Cell International ◽

10.1186/s12935-021-02097-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Luyao Wu ◽

Yu Ding ◽

Houchao Tong ◽

Xi Zhuang ◽

Jingsheng Cai ◽

...

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Noncoding Rna ◽

Animal Experiments ◽

Ectopic Expression ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Papillary Thyroid ◽

Loss Of Function ◽

Functional Roles

Abstract Background Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in various cancers. However, the functional roles of most lncRNA in papillary thyroid cancer (PTC) are not detailly understood. This study aims to investigate the biological function and molecular mechanism of lncRNA Fer-1 like family member 4 (FER1L4) in PTC. Methods The expression of FER1L4 in PTC was determined via operating quantitative real-time PCR assays. Meanwhile, the clinical significance of FER1L4 in patients with PTC was described. The biological functions of FER1L4 on PTC cells were evaluated by gain and loss of function experiments. Moreover, animal experiments were performed to reveal the effect on tumor growth. Subcellular distribution of FER1L4 was determined by fluorescence in situ hybridization and subcellular localization assays. Luciferase reporter assay and RNA immunoprecipitation assay were applied to define the relationship between FER1L4, miR-612, and Cadherin 4 (CDH4). Results Upregulated expression of FER1L4 in PTC tissues was positively correlated with lymph node metastasis (P = 0.020), extrathyroidal extension (P = 0.013) and advanced TNM stages (P = 0.013). In addition, knockdown of FER1L4 suppressed PTC cell proliferation, migration, and invasion, whereas ectopic expression of FER1L4 inversely promoted these processes. Mechanistically, FER1L4 could competitively bind with miR-612 to prevent the degradation of its target gene CDH4. This condition was further confirmed in the rescue assays. Conclusions This study first demonstrates FER1L4 plays an oncogenic role in PTC via a FER1L4-miR-612-CDH4 axis and may provide new therapeutic and diagnostic targets for PTC.

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Low urinary iodine is a protective factor of central lymph node metastasis in papillary thyroid cancer: a cross-sectional study

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02302-6 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Ziyang Zeng ◽

Kang Li ◽

Xianze Wang ◽

Siwen Ouyang ◽

Zimu Zhang ◽

...

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Protective Factor ◽

Urinary Iodine ◽

Iodine Intake ◽

Clinicopathological Features ◽

Papillary Thyroid ◽

Central Lymph Node ◽

High Iodine ◽

Central Lymph

Abstract Background An abrupt increase of thyroid cancer has been witnessed paralleling the supplemented iodine intake in formerly iodine-deficient countries. And increased iodine intake has been linked to the rising incidence rate of papillary thyroid cancer (PTC). However, the correlation between iodine and clinicopathological features of PTC has not been well-characterized. This study aimed to investigate the associations between iodine intake and the clinicopathological features of PTC patients. Methods Three hundred and fifty-nine PTC patients who received surgical treatment in Peking Union Medical College Hospital from May 2015 to November 2020 were retrospectively reviewed. The associations between urinary iodine (UI), urinary iodine/creatinine ratio (UI/U-Cr), and the clinicopathological features of PTC were analyzed. Univariate and multivariate analysis were performed to investigate the relationship between UI level and central lymph node metastasis (CLNM). Results There were no significant differences in UI in different groups according to the variables studied, except that patients with CLNM had higher UI level than CLNM(−) patients. No associations were found between UI/U-Cr and clinicopathological features except variant subtypes (classic/follicular). After dividing patients into high-iodine group and low-iodine group, more patients were found to have CLNM in the high-iodine group (p = 0.02). In addition, younger age, larger tumor size, and classic variant were positively correlated with CLNM (p < 0.05). Univariate analysis showed that insufficient iodine intake (≤ 99 μg/L) was associated with decreased CLNM risk in PTC. And after defining insufficient iodine intake as ≤ 109 μg/L and above requirements as ≥ 190 μg/L, multivariate analysis showed that lower iodine was associated with CLNM in total population of PTC (OR 0.53, 95% CI 0.31–0.91) and in PTC < 1 cm (papillary thyroid microcarcinoma, PTMC) (OR 0.43, 95% CI 0.21–0.87). Conclusions Low iodine was a protective factor for CLNM in papillary thyroid cancer, particularly in those < 1 cm. These results indicated that iodine may not only be an initiator of tumorigenesis, but also a promoter of the development of PTC.

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