Last update 01 Nov 2024

GnRHR x TERT

Last update 01 Nov 2024

Basic Info

Related Targets

GnRHRTERT

Drugs associated with GnRHR x TERT

HS-1002

Target

GnRHR x TERT

Mechanism

GnRHR agonists [+1]

Active Org.

Sungkyunkwan University

Originator Org.

Sungkyunkwan University

Active Indication

Prostatic Cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GnRHR x TERT

100 Translational Medicine associated with GnRHR x TERT

0 Patents (Medical) associated with GnRHR x TERT

Literatures (Medical) associated with GnRHR x TERT

01 Sep 2022·Cancer CytopathologyQ2 · MEDICINE

MicroRNA profiling predicts positive nodal status in papillary thyroid carcinoma in the preoperative setting

Q2 · MEDICINE

Article

Author: Rigutto, Angelica ; Massa, Federica ; Papotti, Mauro ; Zambelli, Vanessa ; Izzo, Stefania ; Troncone, Giancarlo ; Bellevicine, Claudio ; Mortara, Umberto ; Napoli, Francesca ; Volante, Marco ; Rapa, Ida

BACKGROUNDThe molecular characterization of thyroid nodules in cytological samples has so far been focused on discriminating between benign and malignant forms in a purely diagnostic setting. The evidence on the impact of molecular biomarkers to determine the risk of aggressiveness in cytologically “neoplastic” lesions is limited to genomic alterations (such as BRAF and TERT mutations). The aim of our study was to assess the preoperative role of microRNAs (miRNAs) in predicting the nodal status of patients with papillary thyroid cancer.METHODSA pilot series of histological samples of papillary thyroid carcinoma with (6 cases) or without (6 cases) lymph node metastases, matched for other major clinical and pathological features, was analyzed for global miRNA expression in a screening phase. A set of miRNAs was then validated in a series of 63 consecutive cytological samples of papillary carcinomas: 48 pN‐negative and 15 pN‐positive at histology.RESULTSUnsupervised cluster analysis segregated surgical pN‐negative and pN‐positive samples, except for 1 case. The 45 differentially expressed miRNAs in pN‐positive versus pN‐negative cases were predicted to regulate a wide range of cellular pathways, enriched for Wnt, gonadotropin‐releasing hormone receptor, and cerulein/cholecystokinin receptor signaling. In agreement with their profiles in surgical samples, 4 miRNAs of the 10 selected for validation (miR‐154‐3p, miR‐299‐5p, miR‐376a‐3p, and miR‐302E) had a significant differential expression in cytological samples of papillary carcinoma with lymph node metastases and predicted the positive nodal status with a relatively good performance.CONCLUSIONSMiRNA profiling is a potential promising strategy to define papillary carcinoma aggressiveness in the preoperative setting. ;

01 Dec 2021·Cell & BioscienceQ3 · BIOLOGY

Anti-metastatic effect of GV1001 on prostate cancer cells; roles of GnRHR-mediated Gαs-cAMP pathway and AR-YAP1 axis

Q3 · BIOLOGY

ArticleOA

Author: Kim, Hyung Shik ; Kim, Ji Won ; Park, Miso ; Kim, Suntae ; Lim, Sung Chul ; Kang, Keon Wook

AbstractBackgroundGonadotropin-releasing hormone receptor (GnRHR) transmits its signal via two major Gα-proteins, primarily Gαq and Gαi. However, the precise mechanism underlying the functions of Gαs signal in prostate cancer cells is still unclear. We have previously identified that GV1001, a fragment of the human telomerase reverse transcriptase, functions as a biased GnRHR ligand to selectively stimulate the Gαs/cAMP pathway. Here, we tried to reveal the potential mechanisms of which GV1001-stimulated Gαs-cAMP signaling pathway reduces the migration and metastasis of prostate cancer (PCa) cells.MethodsThe expression of epithelial-mesenchymal transition (EMT)-related genes was measured by western-blotting and spheroid formation on ultra-low attachment plate was detected after GV1001 treatment. In vivo Spleen-liver metastasis mouse model was used to explore the inhibitory effect of GV1001 on metastatic ability of PCa and the transwell migration assay was performed to identify whether GV1001 had a suppressive effect on cell migration in vitro. In order to demonstrate the interaction between androgen receptor (AR) and YAP1, co-immunoprecipitation (co-IP), immunofluorescence (IF) staining, chromatin immunoprecipitation (ChIP) were performed in LNCaP cells with and without GV1001 treatment.ResultsGV1001 inhibited expression of EMT-related genes and spheroid formation. GV1001 also suppressed in vivo spleen-liver metastasis of LNCaP cells as well as cell migration in vitro. GV1001 enhanced the phosphorylation of AR and transcription activity of androgen response element reporter gene through cAMP/protein kinase A pathway. Moreover, GV1001 increased Ser-127 phosphorylation of YAP1 and its ubiquitination, and subsequently decreased the levels of AR-YAP1 binding in the promoter region of the CTGF gene. In contrast, both protein and mRNA levels of NKX3.1 known for tumor suppressor gene and AR-coregulator were upregulated by GV1001 in LNCaP cells. YAP1 knockout using CRISPR/Cas9 significantly suppressed the migration ability of LNCaP cells, and GV1001 did not affect the cell migration of YAP1-deficient LNCaP cells. On the contrary, cell migration was more potentiated in LNCaP cells overexpressing YAP5SA, a constitutively active form of YAP1, which was not changed by GV1001 treatment.ConclusionsOverall, this study reveals an essential role of AR-YAP1 in the regulation of PCa cell migration, and provides evidence that GV1001 could be a novel GnRHR ligand to inhibit metastasis of PCa via the Gαs/cAMP pathway.

01 Nov 2002·International journal of molecular medicineQ3 · MEDICINE

GnRH agonist inhibits human telomerase reverse transcriptase mRNA expression in endometrial cancer cells.

Q3 · MEDICINE

Article

Author: Ohama, Koso ; Shigemasa, Kazushi ; Nagai, Nobutaka ; Shiroyama, Yuko ; Oshita, Takafumi ; Mukai, Keiji

We investigated the relationship between the antiproliferative effect of GnRH agonist and telomerase activity using the endometrial cancer cell line HEC-1A. The subjects were 38 endometrial cancer, and 2 atypical endometrial hyperplasia patients. GnRH-R expression was detected using RT-PCR. HEC-1A cells were incubated with 10(-7)-10(-4) M GnRH agonist (leuprolide acetate), and cell proliferation was determined using MTT assay. The telomerase activity was detected by the TRAP assay and expression of human telomerase reverse transcriptase (hTERT) was assessed by RT-PCR. GnRH-R mRNA was detected at 94.7% (36/38) in endometrial cancer and in both of the atypical endometrial hyperplasia and in HEC-1A cells. Cell proliferation of HEC-1A showed significant inhibition at leuprolide acetate concentrations of 10(-6) M or higher compared with untreated control culture (p<0.05). The telomerase activity showed no marked difference compared with untreated culture. However, hTERT mRNA expression showed a decrease in the leuprolide-treated cells. It is suggested that the mechanism of the antitumor effect of GnRH agonist involved the inhibition of hTERT mRNA expression in the endometrial cancer cells.

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