PTEN loss is associated with follicular variant of Middle Eastern papillary thyroid carcinoma

Beg, Shaham; Siraj, Abdul K.; Jehan, Zeenath; Prabakaran, Sarita; Al-Sobhi, Saif S.; Aldawish, Mohammed; Al‐Dayel, Fouad; Al‐Kuraya, Khawla S.

doi:10.1038/bjc.2015.169

Cited by 29 publications

(25 citation statements)

References 41 publications

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“…The probe CEN5q was utilized as reference probe for enumeration. FISH on a TMA was performed as previously described . Tissue samples were classified with a TERT and CEN5q ratio of 1.0 as normal; between 1.0 and 2.0 as having TERT gains; and 2 or over 2 as amplified.…”

Section: Methodsmentioning

confidence: 99%

Telomerase reverse transcriptase mutations are independent predictor of disease‐free survival in Middle Eastern papillary thyroid cancer

Siraj

Divya

et al. 2017

Intl Journal of Cancer

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Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Tumor recurrence occurs in ∼20% of PTCs and some reach advanced stages. Promoter mutation in the telomerase reverse transcriptase (TERT) gene is identified to be a prognostic marker in PTC. However, the contribution of TERT promoter mutation to cancer progression in PTC patients is still not fully understood. In this study, we investigated the incidence of TERT promoter mutations and TERT protein expression and their association with clinicopathological outcomes in a large cohort of PTC samples using direct sequencing technology and immunohistochemistry. Furthermore, two PTC cell lines were utilized to investigate role of TERT mutations in mediating metastasis. Two promoter hotspot mutations C228T and C250T were identified in 18.0% (167/927) of our cohort and were significantly associated with poor 5 years disease-free survival and distant metastasis of PTC. TERT protein overexpression was noted in 20.1% of our PTC cohort and was significantly associated with poor prognostic markers such as older age, extrathyroidal extension and Stage IV tumors. A significant association was also found between TERT overexpression and epithelial-mesenchymal transition (EMT) markers. Functional analysis showed that TERT inhibition reduced cell growth, invasion, migration and angiogenesis in PTC via suppression of EMT in PTC cells. Our results suggest that TERT promoter mutation is an independent predictor of disease-free survival and might drive the metastasis, and downregulation of TERT could potentiate antitumor and antimetastatic activities in PTC.

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Section: Methodsmentioning

confidence: 99%

Telomerase reverse transcriptase mutations are independent predictor of disease‐free survival in Middle Eastern papillary thyroid cancer

Siraj

Divya

et al. 2017

Intl Journal of Cancer

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“…Accruing works have revealed that PTEN is involved in progression of cancers and negatively correlated with AKT signaling in hypopharyngeal carcinoma, non-small cell lung cancer and esophageal squamous cell carcinoma [13][14][15]. Previous study suggested that loss of PTEN is associated with progression of papillary thyroid cancer [16]. In this study, we sought to investigate the roles of miR-17-5p and PTEN in thyroid cancer progression and explore the potential interaction between miR-17-5p and PTEN/AKT/mechanistic target of rapamycin (mTOR) signaling pathway.…”

mentioning

confidence: 99%

miR-17-5p knockdown inhibits proliferation, autophagy and promotes apoptosis in thyroid cancer via targeting PTEN

Shi¹,

Liu²,

Li³

et al. 2020

neo

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Thyroid cancer is one common endocrine malignancy with various pathological types. MicroRNAs (miRNAs) play essential roles in development, prognosis and treatment of thyroid cancer. However, the role of miR-17-5p in thyroid cancer progression and its mechanism remain poorly understood. The expressions of miR-17-5p and phosphatase and tensin homolog (PTEN) were measured in thyroid cancer tissues and cells by quantitative real-time polymerase chain reaction or western blot. Cell proliferation and apoptosis were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay and flow cytometry, respectively. The protein levels of biomarkers in autophagy or protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway were analyzed by western blot. The interaction between miR-17-5p and PTEN was probed by luciferase activity assay. We found that miR-17-5p expression was elevated and PTEN level was reduced in thyroid cancer tissues and cells compared with their corresponding controls. Knockdown of miR-17-5p or overexpression of PTEN suppressed cell proliferation and autophagy but promoted apoptosis in thyroid cancer cells. PTEN was indicated as a target of miR-17-5p and its interference reversed abrogation of miR-17-5p-mediated inhibition of proliferation and autophagy and increase of apoptosis. Moreover, downregulation of miR-17-5p impeded the activation of AKT/mTOR pathway in thyroid cancer cells, which was attenuated by silencing PTEN. Our data supported that knockdown of miR-17-5p upregulated PTEN expression, therefore leading to suppression of the malignancy of thyroid cancer and inactivation of AKT/mTOR pathway, providing a novel avenue for treatment of thyroid cancer.

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“…However, PTEN is a well-known tumor suppressor gene, and loss of PTEN expression isassociated with aggressive behavior and poor prognosis in cancer [ 19 ]. PTEN-deleted mice easily developed malignant tumors [ 20 ]. FOXO1/3 and PTEN depletion in granulosa cells also promoted ovarian granulosa cell tumor development [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Lentiviral-Mediated Short Hairpin RNA Knockdown of MTDHInhibits Cell Growth and Induces Apoptosis by Regulatingthe PTEN/AKT Pathway in Hepatocellular Carcinoma

Ou²,

Dai

et al. 2015

IJMS

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The activation of oncogenes and the loss of tumor suppressor genes are believed to play critical roles in the pathogenesis of human hepatocellular carcinoma (HCC). Metaherin (MTDH), also called astrocyte elevated gene-1 (AEG-1), is frequently amplified in a variety of cancers, but the roles of MTDH with regard to growth and apoptosis in HCC have not yet been studied. In the present study, we first analyzed the expression of MTDH in HCC samples. We found that MTDH protein levels are higher in most HCC cancerous tissues compared with their matched adjacent non-tumor tissues. Additionally, the MTDH mRNA was also higher in HCC tissues compared to their matched adjacent non-tumor tissues. Knockdown of the endogenous MTDH using small interfering RNA further showed that deficiency of MTDH suppressed cell growth and caused apoptosis in HCC cells. Knockdown MTDH promoted PTEN and p53 expression in HCC cells and inhibited AKT phosphorylation. Knockdown MTDH also inhibited tumor growth in vivo. All these results indicated that MTDH protein levels in most HCC tissues are higher than non-tumor tissues, and knockdown of MTDH inhibited growth and induced apoptosis in HCC cells through the activation of PTEN. Therefore, MTDH might be an effective targeted therapy gene for HCC.

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PTEN loss is associated with follicular variant of Middle Eastern papillary thyroid carcinoma

Cited by 29 publications

References 41 publications

Telomerase reverse transcriptase mutations are independent predictor of disease‐free survival in Middle Eastern papillary thyroid cancer

Telomerase reverse transcriptase mutations are independent predictor of disease‐free survival in Middle Eastern papillary thyroid cancer

miR-17-5p knockdown inhibits proliferation, autophagy and promotes apoptosis in thyroid cancer via targeting PTEN

Lentiviral-Mediated Short Hairpin RNA Knockdown of MTDHInhibits Cell Growth and Induces Apoptosis by Regulatingthe PTEN/AKT Pathway in Hepatocellular Carcinoma

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