RUNX3 Promotes the Tumorigenic Phenotype in KGN, a Human Granulosa Cell Tumor-Derived Cell Line

Chen, Huachen; Crosley, Powel; Azad, Abul Kalam; Gupta, Nidhi; Gokul, Nisha; Xu, Zhihua; Weinfeld, Michael; Postovit, Lynne-Marie; Pangas, Stephanie A.; Hitt, Mary; Fu, YangXin

doi:10.3390/ijms20143471

Cited by 8 publications

(9 citation statements)

References 52 publications

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“…Recently it has been demonstrated that RUNX3 when associates with MYC functions as a tumor promoter whereas; acts as a tumor suppressor when interacts with p53 [47]. Various other studies have demonstrated the oncogenic role of RUNX3 [46,[48][49][50][51][52][53][54].…”

Section: Discussionmentioning

confidence: 99%

Elevated expression of RUNX3 co-expressing with EZH2 in esophageal cancer patients from India

Rehman¹,

Iqbal

Sattar³

et al. 2020

Cancer Cell Int

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Background Runt related transcription factor3 (RUNX3) is considered as a tumor suppressor gene (TSG) that functions through the TGF-β dependent apoptosis. Promoter methylation of the CpG islands of RUNX3 and overexpression of enhancer of zeste homolog 2 (EZH2) has been suggested to downregulate RUNX3 in cancer. Methods Here, we studied the expression of RUNX3 and EZH2 in 58 esophageal tumors along with paired adjacent normal tissue. mRNA levels, protein expressions and cellular localizations of EZH2 and RUNX3 were analyzed using real-time PCR and immunohistochemistry, respectively. DNA methylation was further assessed by the methylation specific-PCR. Results Compared to normal tissue, a significant increase in expression of RUNX3 mRNA in 31/57 patient’s tumor tissue (p < 0.04) was observed. The expression of EZH2 was found to be upregulated compared to normal, and a significant positive correlation between EZH2 and RUNX3 expression was observed (p = 0.002). 22 of the 27 unmethylated cases at the promoter region of the RUNX3 had elevated RUNX3 protein expression (p < 0.001). Conclusion The data presented in this study provide new insights into the biology of RUNX3 and highlights the need to revisit our current understanding of the role of RUNX3 in cancer.

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Section: Discussionmentioning

confidence: 99%

Elevated expression of RUNX3 co-expressing with EZH2 in esophageal cancer patients from India

Rehman¹,

Iqbal

Sattar³

et al. 2020

Cancer Cell Int

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“…The classification of COV434 as a GCT-derived cell line has been questioned. Recent studies show that this cell line was likely derived from a small-cell carcinoma of the ovary hypercalcemic-type (SCCOHT) [105][106][107]. The cell of origin of these tumors is unknown, with reports postulating they are likely derived from the germ cells [108].…”

Section: Gct-derived Cell Linesmentioning

confidence: 99%

“…SCCOHT are characterized by the loss of both SMARCA2 and SMARCA4, which are also not expressed in COV434 cells [105,107]. Moreover, the lack of expression of RUNX2 and high expression of RUNX3 in COV434 suggests that these cells do not represent primary jGCT [106]. Noticeably, the study of Karnezis et al indicates that COV434 cell line has all morphological, immunohistochemical, genetic and clinical Genetics and Mutational Landscape of Ovarian Sex Cord-Stromal Tumors DOI: http://dx.doi.org/10.5772/intechopen.97540 characteristics of SCCOHT [107].…”

Section: Gct-derived Cell Linesmentioning

confidence: 99%

Genetics and Mutational Landscape of Ovarian Sex Cord-Stromal Tumors

Nguyen¹,

Tran²,

Choo³

et al. 2021

Ovarian Cancer - Updates in Tumour Biology and Therapeutics [Working Title]

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Ovarian sex cord-stromal tumors (SCST) are uncommon tumors accounting for approximately 8% of all ovarian malignancies. By far, the most common are granulosa cell tumors (GCT) which represent approximately 90% of SCST. SCST are also found in the hereditary syndromes: Peutz-Jeghers syndrome, Ollier disease and Maffucci syndrome, and DICER1 syndrome. Key genomic and genetic events contributing to their pathogenesis have been the focus of recent studies. Most of the genomic studies have been limited to GCT which have identified a number of recurring chromosomal abnormalities (monosomy and trisomy), although their contribution to pathogenesis remains unclear. Recurrent DICER1 mutations are reported in non-hereditary cases of Sertoli cell and Sertoli–Leydig cell tumors (SLCT), while recurrent somatic mutations in both the juvenile (jGCT) and adult forms of GCT (aGCT) have also been reported. Approximately 30% of jGCT contain a somatic mutation in the gsp oncogene, while a further 60% have activating mutations or duplications in the AKT gene. For aGCT, a well characterized mutation in the FOXL2 transcription factor (FOXL2 C134W) is found in the majority of tumors (primary and recurrent), arguably defining the disease. A further mutation in the human telomerase promoter appears to be an important driver for recurrent disease in aGCT. However, despite several studies involving next generation sequencing, the molecular events that determine the stage, behavior and prognosis of aGCT still remain to be determined. Further, there is a need for these studies to be expanded to other SCST in order to identify potential targets for personalized medicine.

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“…Loss of Runx3 expression has also frequently been found in melanoma cells as compared to melanocytes, and there is a good negative correlation between Runx3 expression and melanoma malignancy [ 40 ]. In addition, many functional studies have demonstrated that Runx3 is a tumor suppressor in many types of cancers but is a tumor promoter in other types [ 37 , 38 , 39 , 41 , 42 , 43 , 44 ].…”

Section: Introductionmentioning

confidence: 99%

Runx3 Induces a Cell Shape Change and Suppresses Migration and Metastasis of Melanoma Cells by Altering a Transcriptional Profile

Wang

Zhang

Cui

et al. 2021

IJMS

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Runt-related transcription factor-3 (Runx3) is a tumor suppressor, and its contribution to melanoma progression remains unclear. We previously demonstrated that Runx3 re-expression in B16-F10 melanoma cells changed their shape and attenuated their migration. In this study, we found that Runx3 re-expression in B16-F10 cells also suppressed their pulmonary metastasis. We performed microarray analysis and uncovered an altered transcriptional profile underlying the cell shape change and the suppression of migration and metastasis. This altered transcriptional profile was rich in Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) annotations relevant to adhesion and the actin cytoskeleton and included differentially expressed genes for some major extracellular matrix (ECM) proteins as well as genes that were inversely associated with the increase in the metastatic potential of B16-F10 cells compared to B16-F0 melanoma cells. Further, we found that this altered transcriptional profile could have prognostic value, as evidenced by myelin and lymphocyte protein (MAL) and vilin-like (VILL). Finally, Mal gene expression was correlated with metastatic potential among the cells and was targeted by histone deacetylase (HDAC) inhibitors in B16-F10 cells, and the knockdown of Mal gene expression in B16-F0 cells changed their shape and enhanced the migratory and invasive traits of their metastasis. Our study suggests that self-entrapping of metastatic Runx3-negative melanoma cells via adhesion and the actin cytoskeleton could be a powerful therapeutic strategy.

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RUNX3 Promotes the Tumorigenic Phenotype in KGN, a Human Granulosa Cell Tumor-Derived Cell Line

Cited by 8 publications

References 52 publications

Elevated expression of RUNX3 co-expressing with EZH2 in esophageal cancer patients from India

Elevated expression of RUNX3 co-expressing with EZH2 in esophageal cancer patients from India

Genetics and Mutational Landscape of Ovarian Sex Cord-Stromal Tumors

Runx3 Induces a Cell Shape Change and Suppresses Migration and Metastasis of Melanoma Cells by Altering a Transcriptional Profile

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