Long Non-Coding RNAs in Thyroid Cancer: Implications for Pathogenesis, Diagnosis, and Therapy

Mahmoudian-Sani, Mohammad-Reza; Jalali, Akram; Jamshidi, Mohammad; Moridi, Heresh; Alghasi, Arash; Shojaeian, Ali; Mobini, Gholam-Reza

doi:10.1159/000495151

Cited by 63 publications

(52 citation statements)

References 72 publications

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“…At present, the speci city of GBC diagnosis is relatively low, and patients with advanced stage have poor progression and high mortality. It is well documented that lncRNAs and miRNAs are potential therapeutic targets for various cancers [23]. Herein, we aimed to explore regulatory mechanism between UCA1 and miR-613 in GBC.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of Long Non-coding RNA UCA1 Represses Gallbladder Cancer Advancement by Regulating SPOCK1 Expression via Sponging miR-613

Zhang

Chen

et al. 2020

Preprint

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OBJECTIVE : Patients with advanced gallbladder cancer (GBC) have a lower 5-year survival rate. Long non-coding RNA urothelial carcinoma associated 1 (UCA1) and miR-613 are involved in the progression of various cancers. This study was to explore the regulatory mechanism between UCA1 and miR-613 in GBC. METHODS: The expression levels of UCA1, miR-613, and SPOCK1 mRNA were detected using qRT-PCR. Cell proliferation, migration, invasion, and apoptosis were determined with MTT, transwell, or flow cytometry assays. The levels of SPOCK1 protein, Bax, cleaved-casp-3, and Bcl-2 were determined by western blot analysis. The relationship between miR-613 and UCA1 or SPOCK1 was verified via dual-luciferase reporter and/or RNA immunoprecipitation (RIP) assays. The role of UCA1 in vivo was confirmed by xenograft assay. RESULTS: UCA1 and SPOCK1 were upregulated while miR-613 was downregulated in GBC tissues and cells. UCA1 silencing blocked tumor growth in vivo, impeded cell proliferation, migration, invasion, and induced cell apoptosis in GBC cells in vitro. Notably, UCA1 acted as a sponge for miR-613, which targeted SPOCK1 in GBC cells. Moreover, miR-613 repressed cell proliferation, migration, invasion, and accelerated cell apoptosis in GBC cells. UCA1 enhancement reversed miR-613 mimic-mediated influence on proliferation, migration, invasion, and apoptosis of GBC cells. UCA1 regulated SPOCK1 expression through miR-613. Furthermore, SPOCK1 elevation overturned UCA1 silencing-mediated the malignant behaviors of GBC cells. CONCLUSION: UCA1 knockdown suppressed GBC progression via downregulating SPOCK1 via sponging miR-613, providing an evidence for UCA1 as a target for GBC treatment.

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Section: Discussionmentioning

confidence: 99%

Knockdown of Long Non-coding RNA UCA1 Represses Gallbladder Cancer Advancement by Regulating SPOCK1 Expression via Sponging miR-613

Zhang

Chen

et al. 2020

Preprint

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“…It is commonly observed that alteration of lncRNAs occurred in thyroid cancer [31]. A series of lncRNAs have been found to play oncogenic or suppressor roles in thyroid cancer, of which some are suggested as potential therapeutic targets [31][32][33][34]. To our knowledge, it is the rst time that the differential lncRNAs have been screened out among NTs, PTCs and DDTCs from the FUSCC cohort to identify a lncRNA biomarker associated with dedifferentiation of thyroid cancer, which was speci cally altered in ATC, and then was con rmed to regulate the malignancy of ATC.…”

Section: Discussionmentioning

confidence: 99%

LINC00886, as a Biomarker Indicative of Thyroid Cancer Dedifferentiation, Negatively Regulates the Malignancy in Anaplastic Thyroid Cancer

Ma¹,

Luo²,

Xu³

et al. 2020

Preprint

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Backgroud: Anaplastic thyroid cancer (ATC) is the most aggressive type of thyroid cancer. This study aimed to identify a long non-cdoing RNA (lncRNA) as a specific biomarker associated with ATC, and further investigated its biological function and molecular mechanism underlying regulation of malignancy in ATC.Methods: We searched for lncRNAs associated with dedifferentiation and screened out specific lncRNAs significantly deregulated in ATC by using transcriptome data of dedifferentiation cancers from Fudan University Shanghai Cancer Center (FUSCC) and the Gene Expression Omnibus (GEO) database. The above lncRNAs were analyzed to identify a useful biomarker in thyroid cancer patients from the FUSCC, GEO and The Cancer Genome Atlas, which was further investigated for its functional roles and molecular mechanism in ATC in vitro.Results: The clinicopathological association analyses revealed that LINC00886 was correlated with thyroid cancer dedifferentiation and significantly suppressed in ATC. In vitro, LINC00886 was confirmed to negatively regulate cell proliferation, colony formation and cell migration and invasion of ATC. LINC00886 physically interacted with protein kinase R (PKR) and affected its stability through ubiquitin/proteasome-dependent degradation pathway in the ATC cell. Decreased PKR caused by LINC00886 downregulation, enhanced the activity of eukaryotic initiation factor 2α (eIF2α) via reducing the phosphorylation of eIF2α and thus promoted protein synthesis to maintain the ATC malignancy. Conclusions: Our findings identify LINC00886 as a novel biomarker of thyroid cancer and suggest that the LINC00886/PKR/eIF2α signaling axis is a potential therapeutic target in ATC.

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“…Long noncoding RNAs (lncRNAs) refer to the type of noncoding RNA that is derived from genome-encoded transcripts with lengths longer than 200 RNA nucleotides (3). Recent studies suggest it may be directly involved in the regulation of development of tumor cells (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

OTUD6B-AS1 Inhibits Viability, Migration, and Invasion of Thyroid Carcinoma by Targeting miR-183-5p and miR-21

et al. 2020

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Background: The long noncoding RNA (lncRNA) functions as a regulator of initiation, progression, and metastasis of thyroid carcinomas. lncRNA OTUD6B antisense RNA 1 (OTUD6B-AS1) is a tumor-suppressive noncoding RNA in clear cell renal cell carcinoma. The role of OTUD6B-AS1 in thyroid carcinomas has not been reported yet. We aim to investigate the expression and biological functions of OTUD6B-AS1 in thyroid carcinomas. Methods:The expression level of OTUD6B-AS1 was measured in 60 paired human thyroid carcinoma tissues and corresponding adjacent normal thyroid tissues. The correlations between the OTUD6B-AS1 expression levels and clinicopathological features were evaluated using the Mann-Whitney test. The effects of OTUD6B-AS1 on thyroid carcinoma cells were determined via the MTT and transwell assays. The potential targets of OTUD6B-AS1 were screened using the online programs OncomiR and StarBase 3.0, and the LncBase Predicted v.2. Luciferase reporter assay was used to confirm the interactions between OTUD6B-AS1 and its potential targets.Results: OTUD6B-AS1 was downregulated in thyroid carcinoma tissue samples. The expression of OTUD6B-AS1 correlated with tumor size, clinical stage, and lymphatic metastasis of thyroid carcinoma. Overexpression of OTUD6B-AS1 significantly decreased the viability, migration, and invasion of thyroid carcinoma cells. Online programs predicted miR-183-5p and miR-21 as potential targets of OTUD6B-AS1. Luciferase reporter assays showed miR-183-5p and miR-21 bound to OTUD6B-AS1. Moreover, overexpression of miR-183-5p and miR-21 compromised the inhibitory effects of OTUD6B-AS1 on viability, migration, and invasion of thyroid carcinoma cells.Conclusions: Taken together, our findings present in vitro evidence of lncRNA OTUD6B-AS1 as a tumor suppressor in thyroid carcinomas. OTUD6B-AS1 inhibits viability, migration, and invasion of thyroid carcinoma by targeting miR-183-5p and miR-21.

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Long Non-Coding RNAs in Thyroid Cancer: Implications for Pathogenesis, Diagnosis, and Therapy

Cited by 63 publications

References 72 publications

Knockdown of Long Non-coding RNA UCA1 Represses Gallbladder Cancer Advancement by Regulating SPOCK1 Expression via Sponging miR-613

Knockdown of Long Non-coding RNA UCA1 Represses Gallbladder Cancer Advancement by Regulating SPOCK1 Expression via Sponging miR-613

LINC00886, as a Biomarker Indicative of Thyroid Cancer Dedifferentiation, Negatively Regulates the Malignancy in Anaplastic Thyroid Cancer

OTUD6B-AS1 Inhibits Viability, Migration, and Invasion of Thyroid Carcinoma by Targeting miR-183-5p and miR-21

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