PI3K/AKT Pathway and Its Mediators in Thyroid Carcinomas

Nozhat, Zahra; Hedayati, Mehdi

doi:10.1007/s40291-015-0175-y

Cited by 73 publications

(61 citation statements)

References 117 publications

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“…BDNF can also bind to its major receptor, tropomyosin-related receptor kinase B (TrkB), leading to the activations of multiple downstream signal pathways, such as PI3K/AKT, RAS/ERK, PLC/PKC, AMPK/ACC, and JAK/STAT pathways [29], which promote tumorigenesis. Specifically, PI3K/AKT pathway has been widely reported to be involved in thyroid cancer progression and development [30, 31]. Several miRNAs, such as miR-107 [32], miR-15a-5p [33], miR-204 [34], and miR-206 [35], inhibit cancer progression by suppressing BDNF.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-497 inhibits thyroid cancer tumor growth and invasion by suppressing BDNF

et al. 2016

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miR-497 reportedly plays critical roles in tumor development and progression in many types of cancers. We therefore investigated the function and underlying mechanism of miR-497 in thyroid cancer. We found that miR-497 is downregulated in thyroid cancer tissues, and that miR-497 levels are negatively correlated with advanced clinical stage and lymph node metastasis. Overexpressed miR-497 suppressed thyroid cancer cell proliferation, colony formation, migration, and invasion in vitro, and inhibited tumorigenesis in vivo. Moreover, brain-derived neurotrophic factor (BDNF), a known oncogene, was confirmed as a direct target of miR-497 in thyroid cancer cells. miR-497 overexpression suppressed BDNF expression and its downstream pathway(PI3K/AKT)in vitro and in vivo. BDNF levels were upregulated and inversely correlated with miR-497 levels in human thyroid cancer specimens. Rescue experiments showed that forced overexpression of BDNF effectively reversed the tumor suppressive functions of miR-497. These results show that miR-497 is a thyroid cancer tumor suppressor that acts by repressing BDNF.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-497 inhibits thyroid cancer tumor growth and invasion by suppressing BDNF

et al. 2016

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“…22 Moreover, studies have revealed that phosphoinositide 3-kinase AKT (PI3K-AKT) pathway also drived carcinogenesis of PTC. 23 Cell proliferation plays an important role in tumor progression and prognosis. Activation of PI3K-AKT signaling pathway results in high cell proliferation and vascularity.…”

Section: Introductionmentioning

confidence: 99%

<p>ANGPTL4 Promotes the Proliferation of Papillary Thyroid Cancer via AKT Pathway</p>

Yang¹,

Wang²,

Sun³

et al. 2020

OTT

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Although papillary thyroid carcinoma (PTC) is associated with a generally favorable prognosis, about 15% of patients present recurrence and distant metastasis in the next decade leading to death. Angiopoietin-like 4 (ANGPTL4) is secreted to circulation and belongs to the angiopoietin-like proteins. The expression of ANGPTL4 was increased in several solid tumor tissues compared to corresponding paracancerous tissues. ANGPTL4 was identified as pro-tumorigenic protein, including stimulating tumor cell growth, promoting tumor metastasis. However, the clinical significance and biological function of ANGPTL4 in PTC is still unclear. Hence, the purpose of this study was to evaluate the role of ANGPTL4 in PTC, investigating the possibility of whether ANGPTL4 could become a novel target for PTC therapy. Methods: We investigated the expression level of ANGPTL4 and pAKT in PTC and paracancerous tissue by immunohistochemistry. We determined the effect of ANGPTL4 in PTC cell proliferation through cell counting kit-8 (CCK-8) and cell cycle by flow cytometry analysis. Furthermore, the correlation between ANGPTL4 expression levels and PTC cell proliferation from the TCGA data set was analyzed by GSEA. We explored the role of ANGPTL4 on the phosphorylation of AKT and proliferation in PTC cells via overexpression or knockdown assays and AKT inhibitor assay. Results: In the present study, we found that ANGPTL4 was highly expressed in both protein and mRNA level in PTC compared with adjacent noncancerous tissues or benign nodule. ANGPTL4 expression increased according to thyroid tumor progression. ANGPTL4 level was positively correlated with the size of PTC. ANGPTL4 increased cell proliferation and decreased cell cycle arrest of PTC. Knockdown of ANGPTL4 inhibited the phosphorylation of AKT. ANGPTL4 regulated PTC cell proliferation through AKT signaling pathway. Conclusion: Our findings suggested that ANGPTL4 was increased in PTC compared with adjacent noncancerous tissues, and ANGPTL4 increased cell proliferation and inhibited cell cycle arrest in PTC cells via promoting AKT phosphorylation. The study may provide fundamental information to suggest its suitability as a target for the treatment of PTC.

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“…Among the other altered signal transduction pathways, the FoxO and PI3K-Akt signaling pathway is known to be involved in thyroid cancer (Zaballos & Santisteban 2013, Gunda et al 2014, Sun et al 2015, Nozhat & Hedayati 2016. However, previous high frequency genetic studies have reported the activation of somatic alterations of genes encoding effectors in the MAPK signaling pathway, including point mutations in…”

Section: :10mentioning

confidence: 99%

Differences in miRNA expression profiles between wild-type and mutated NIFTPs

Denaro¹,

Ugolini²,

Poma³

et al. 2017

Endocrine-Related Cancer

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Noninvasive encapsulated follicular variants of papillary thyroid carcinomas have been recently reclassified as noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs). NIFTPs exhibit a behavior that is very close to that of follicular adenomas but different from the infiltrative and invasive follicular variants of papillary thyroid carcinomas (FVPTCs). The importance of miRNAs to carcinogenesis has been reported in recent years. miRNAs seem to be promising diagnostic and prognostic molecular markers for thyroid cancer, and the combination of miRNA expression and mutational status might improve cytological diagnosis. The aim of the present study was to evaluate the miRNA expression profile in wild-type, or-mutated NIFTPs, infiltrative and invasive FVPTCs, and follicular adenomas using the nCounter miRNA Expression assay (NanoString Technologies). To identify the significant Kyoto Encyclopedia of Genes and Genomes (KEGG) molecular pathways associated with deregulated miRNAs, we used the union of pathways option in DNA Intelligent Analysis (DIANA) miRPath software. We have shown that the miRNA expression profiles of wild-type and mutated NIFTPs could be different. The expression profile of wild-type NIFTPs seems comparable to that of follicular adenomas, whereas mutated NIFTPs have an expression profile similar to that of infiltrative and invasive FVPTCs. The upregulation of 4 miRNAs (miR-221-5p, miR-221-3p, miR-222-3p, miR-146b-5p) and the downregulation of 8 miRNAs (miR-181a-3p, miR-28-5p, miR-363-3p, miR-342-3p, miR-1285-5p, miR-152-3p, miR-25-3p, miR-30e-3) in mutated NIFTPs compared to wild-type ones suggest a potential invasive-like phenotype by deregulating the specific pathways involved in cell adhesion and cell migration (Hippo signaling pathway, ECM-receptor interaction, adherens junction, regulation of actin cytoskeleton, fatty acid biosynthesis and metabolism).

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PI3K/AKT Pathway and Its Mediators in Thyroid Carcinomas

Cited by 73 publications

References 117 publications

MicroRNA-497 inhibits thyroid cancer tumor growth and invasion by suppressing BDNF

MicroRNA-497 inhibits thyroid cancer tumor growth and invasion by suppressing BDNF

<p>ANGPTL4 Promotes the Proliferation of Papillary Thyroid Cancer via AKT Pathway</p>

Differences in miRNA expression profiles between wild-type and mutated NIFTPs

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