MicroRNAs in Medullary Thyroid Carcinoma: A State of the Art Review of the Regulatory Mechanisms and Future Perspectives

Galuppini, Francesca; Censi, Simona; Moro, Michele; Carraro, S.; Sbaraglia, Marta; Iacobone, Maurizio; Fassan, Matteo; Mian, Caterina; Pennelli, Gianmaria

doi:10.3390/cells10040955

Cited by 13 publications

(5 citation statements)

References 107 publications

(125 reference statements)

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“…The role of RET in MTC progression, particularly in metastasis, remains incompletely characterised [3]. Recent research has increasingly focused on microRNAs and genes that regulate cell cycle and apoptosis to understand the complexities of MTC progression, as well as other neoplasms [2,4].…”

Section: Introductionmentioning

confidence: 99%

Effects of boric acid on proliferation, apoptosis and miRNAs in medullary thyroid cancer cells

Yıldırım,

Seçme,

Dodurga

et al. 2024

Preprint

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Background: Medullary thyroid cancer (MTC) is a highly aggressive and chemotherapy-resistant cancer that originates from the thyroid's parafollicular C cells. Due to its resistance to conventional treatments, alternative treatments such as boric acid have been explored.Boric acid, a boron-based compound, has demonstrated anticarcinogenic effects, making it a potential candidate for MTC treatment. Methods: Cell viability was assessed using the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay. Total RNA was extracted using Trizol reagent for gene expression and microRNA (miRNA) analysis via reverse transcription-polymerase chain reaction (RT-PCR). The extent of apoptosis induced by boric acid was determined using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Colony formation assays were also conducted to evaluate the impact of boric acid on the colony-forming ability of MTC cells. Results: At 48 hours, The 50% inhibitory concentration (IC50) of boric acid was found to be 35 μM. Treatment with boric acid resulted in significant modulation of apoptosis-related genes and miRNAs, including increased expression of NOXA, apoptotic protease activating factor 1 (APAF-1), Bcl-2-associated X protein (Bax), caspase-3,and caspase-9, which are associated with apoptosis. In contrast, the expression of B-cell lymphoma 2 (Bcl2) , B‐ cell lymphoma‐ extra-large (Bcl-xl) and microRNA-21 (miR-21), which are linked to the aggressiveness of MTC, was significantly reduced. The TUNEL assay indicated a 14% apoptosis rate, and there was a 67.9% reduction in colony formation, as shown by the colony formation assay. Conclusion: Our study suggests that boric acid may have anticancer activity in MTC by modulating apoptotic pathways. These findings suggest that boric acid could be a potential therapeutic agent for MTC, and possibly for other malignancies with similar pathogenic mechanisms.

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Section: Introductionmentioning

confidence: 99%

Effects of boric acid on proliferation, apoptosis and miRNAs in medullary thyroid cancer cells

Yıldırım,

Seçme,

Dodurga

et al. 2024

Preprint

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show abstract

“…In this context, in recent years, studies on MicroRNAs and genes related to cell cycle and apoptosis have been very much to reveal progression, tumor development and similar in MTC and other types of cancer [2,4].…”

Section: Introductionmentioning

confidence: 99%

Effects of boric acid on invasion, migration, proliferation, apoptosis and miRNAs in medullary thyroid cancer cells

Yıldırım

Seçme

Dodurga

et al. 2023

Preprint

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Background Medullary thyroid cancer (MTC) is an aggressive, chemoresistant form originating from the thyroid parafollicular C cells, has spurred interest in alternative treatments like boric acid, a boron-based compound has demonstrated anti-carcinogenic effects. Materials and Methods Cell viability were determined using 2,3-bis(2-methoxy-4 nitro-5- sulfophenyl- 2H-tetrazolium- 5-carboxanilide (XTT) assay.. Total RNA was isolated with Trizol reagent for gene and miRNA analysis via reverse transcription polymerase chain reaction (RT-PCR). Terminal deoxynucleotidyl transferase dUTP nick end labeling assay (TUNEL) and comet assays evaluated boric acid's impact on apoptosis and genotoxicity, respectively. We also examined its influence on cell invasion, colony formation, and migration using matrigel- chamber, colony formation, and wound healing assays. Results 50% lethal dose (IC50) of boric acid was 35 µM at 48 hours. Real-time PCR showed changes at apoptosis-related genes, and miRNAs post-treatment. Significant increases in the expression of NOXA, apoptotic protease activating factor 1 (APAF-1), Bcl-2-associated X protein (Bax), caspase-3, and caspase-9, which are associated with apoptosis, were observed. Additionally, the expression of B-cell lymphoma 2 (bcl2), B- cell lymphoma‐ extra-large (bcl-xl), and microRNA-21 (miR-21), which are linked to the aggressiveness of MTC, was significantly reduced. The TUNEL assay revealed a 14% apoptosis rate, while assays showed a 30.8% decrease in cell invasion, a 67.9% decrease in colony formation, reduced cell migration, and increased DNA breaks post-treatment. Conclusions In conclusion, our findings suggest that boric acid may have potential as an anticancer agent in medullary thyroid cancer and other cancers with similar mechanisms.

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“…Galuppini et al [ 40 ] leaned toward the use of circulating miRNAs as biomarkers. They are fragments of 20–22 base pair long, noncoding RNA that play a role in cancer pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

“…There is some correlation between the expression of specific miRNAs and tumor genotype. The downregulation of miR-224, miR-127 and miR-129-5p and the upregulation of miR-183, miR-153-3p, miR-144 and miR-34a have been demonstrated in RET-positive patients [ 40 ]. This knowledge can be helpful in determining disease prognosis.…”

Section: Introductionmentioning

confidence: 99%

Update on the Diagnosis and Management of Medullary Thyroid Cancer: What Has Changed in Recent Years?

Kaliszewski

Ludwig

et al. 2022

Cancers

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Medullary thyroid carcinoma (MTC) is a neoplasm originating from parafollicular C cells. MTC is a rare disease, but its prognosis is less favorable than that of well-differentiated thyroid cancers. To improve the prognosis of patients with MTC, early diagnosis and prompt therapeutic management are crucial. In the following paper, recent advances in laboratory and imaging diagnostics and also pharmacological and surgical therapies of MTC are discussed. Currently, a thriving direction of development for laboratory diagnostics is immunohistochemistry. The primary imaging modality in the diagnosis of MTC is the ultrasound, but opportunities for development are seen primarily in nuclear medicine techniques. Surgical management is the primary method of treating MTCs. There are numerous publications concerning the stratification of particular lymph node compartments for removal. With the introduction of more effective methods of intraoperative parathyroid identification, the complication rate of surgical treatment may be reduced. The currently used pharmacotherapy is characterized by high toxicity. Moreover, the main limitation of current pharmacotherapy is the development of drug resistance. Currently, there is ongoing research on the use of tyrosine kinase inhibitors (TKIs), highly specific RET inhibitors, radiotherapy and immunotherapy. These new therapies may improve the prognosis of patients with MTCs.

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MicroRNAs in Medullary Thyroid Carcinoma: A State of the Art Review of the Regulatory Mechanisms and Future Perspectives

Cited by 13 publications

References 107 publications

Effects of boric acid on proliferation, apoptosis and miRNAs in medullary thyroid cancer cells

Effects of boric acid on proliferation, apoptosis and miRNAs in medullary thyroid cancer cells

Effects of boric acid on invasion, migration, proliferation, apoptosis and miRNAs in medullary thyroid cancer cells

Update on the Diagnosis and Management of Medullary Thyroid Cancer: What Has Changed in Recent Years?

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