RBPJ and MAML3: Potential Therapeutic Targets for Small Cell Lung Cancer

Onishi, Hideya; Ichimiya, Shu; Yanai, Kosuke; Umebayashi, Masayo; Nakamura, Katsuya; Yamasaki, Akio; Imaizumi, Akira; Nagai, Sonoko; Murahashi, Mutsunori; Ogata, Hisanobu; Morisaki, T.

doi:10.21873/anticanres.12758

Cited by 17 publications

(9 citation statements)

References 4 publications

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“…Glioma‐associated oncogene proteins 1, 2, and 3 (Gli1, Gli2, and Gli3) belong to the family of Krüppel‐like transcription factors with C2H2‐Zn finger DNA‐binding domains. Gli1, Gli2, and Gli3 are the key transcriptional effectors of the hedgehog (Hh) signaling pathway (Briscoe & Therond, ; Hui & Angers, ), which is a morphogenic‐signaling pathway reported as being involved in the development of multiple tumors (Lee, Lee, & Oh, ; Onishi et al, ; Sadam et al, ). All of the Gli proteins contribute to tumor progression by inhibiting tumor cell apoptosis, stimulating cell cycle progression, and promoting tumor cell invasion and metastasis.…”

Section: Introductionmentioning

confidence: 99%

FOXE1 supports the tumor promotion of Gli2 on papillary thyroid carcinoma by the Wnt/β‐catenin pathway

Huang

Shen

et al. 2019

Journal Cellular Physiology

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Papillary thyroid carcinoma (PTC) is a common malignancy in thyroid tissue. However, the molecular mechanism of PTC tumor progression remains unknown. The hedgehog (Hh) pathway is thought to play a key role during PTC development. Here we investigate the effects of glioma‐associated oncogene protein‐2 (Gli2), an important transcription factor of the Hh‐signaling pathway, on PTC. Gli2 and forkhead box E1 (FOXE1) protein levels were upregulated in tissues of PTC patients and PTC cell lines. Using the PTC cell line TPC‐1, we show that Gli2 small interfering RNA (siRNA) reduces cell proliferation, migration, and invasion; whereas overexpression of FOXE1 produces the opposite effects. Moreover, Gli2 siRNA inhibited the expression of genes implicated in the Wnt/β‐catenin pathway and that FOXE1 overexpression produces the opposite effects. Thus, it was indicated that Gli2 promoted the proliferation, migration, and invasion of TPC‐1 cells by activating Wnt/β‐catenin and FOXE1 is involved in this process. Xenograft models of PTC were also constructed, the results showed that Gli2 siRNA reduced the rate of tumor growth, FOXE1 levels, and the expression of the Wnt/β‐catenin pathway but FOXE1 overexpression reversed that effects. In conclusion, this study demonstrates that Gli2 promotes the growth of PTC tumors and TPC‐1 cell proliferation, migration, and invasion by activating the Wnt/β‐catenin pathway via FOXE1.

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Section: Introductionmentioning

confidence: 99%

FOXE1 supports the tumor promotion of Gli2 on papillary thyroid carcinoma by the Wnt/β‐catenin pathway

Huang

Shen

et al. 2019

Journal Cellular Physiology

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“…Therefore, we focused on the up-regulated DEGs in CMP which involved in the cell proliferation. MAML3 is a transcriptional co-activator of Notch signaling pathway, contributing to cancer cells proliferation in acute lymphoblastic leukemia [ 39 ] and some solid tumors [ 40 , 41 ]. PLCB1, is a kind of phospholipase C, involving in the phosphoinositide-dependent signal transduction pathway and Wnt signaling pathway.…”

Section: Resultsmentioning

confidence: 99%

Single-cell transcriptomics dissects the transcriptome alterations of hematopoietic stem cells in myelodysplastic neoplasms

Zeng,

Wang,

Dai

et al. 2024

J Transl Med

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Background Myelodysplastic neoplasms (MDS) are myeloid neoplasms characterized by disordered differentiation of hematopoietic stem cells and a predisposition to acute myeloid leukemia (AML). The underline pathogenesis remains unclear. Methods In this study, the trajectory of differentiation and mechanisms of leukemic transformation were explored through bioinformatics analysis of single-cell RNA-Seq data from hematopoietic stem and progenitor cells (HSPCs) in MDS patients. Results Among the HSPC clusters, the proportion of common myeloid progenitor (CMP) was the main cell cluster in the patients with excess blasts (EB)/ secondary AML. Cell cycle analysis indicated the CMP of MDS patients were in an active proliferative state. The genes involved in the cell proliferation, such as MAML3 and PLCB1, were up-regulated in MDS CMP. Further validation analysis indicated that the expression levels of MAML3 and PLCB1 in patients with MDS-EB were significantly higher than those without EB. Patients with high expression of PLCB1 had a higher risk of transformation to AML. PLCB1 inhibitor can suppress proliferation, induce cell cycle arrest, and activate apoptosis of leukemic cells in vitro. Conclusion This study revealed the transcriptomic change of HSPCs in MDS patients along the pseudotime and indicated that PLCB1 plays a key role in the transformation of MDS into leukemia.

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“…TST is mainly localized to mitochondria and catalyzes the conversion of thiosulfate and cyanide to thiocyanate and sulfite [ 55 ]. As molecular switches in regulating the notch response, transcription factor RBPJ involves in the regulation of the progression of a variety of tumors, such as colorectal cancer [ 56 ], lung cancer [ 57 ], hepatocellular carcinoma [ 58 ], glioblastoma [ 59 , 60 ], and prostate cancer [ 61 ]. As a member of the G protein family, GNA11 plays an important role in tumor progression [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Genomic Analysis of Abnormal DNAM Methylation in Parathyroid Tumors

Sun

et al. 2022

International Journal of Endocrinology

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Background. Parathyroid tumors are common endocrine neoplasias associated with primary hyperparathyroidism. Although numerous studies have studied the subject, the predictive value of gene biomarkers nevertheless remains low. Methods. In this study, we performed genomic analysis of abnormal DNA methylation in parathyroid tumors. After data preprocessing, differentially methylated genes were extracted from patients with parathyroid tumors by using t-tests. Results. After refinement of the basic differential methylation, 28241 unique CpGs (634 genes) were identified to be methylated. The methylated genes were primarily involved in 7 GO terms, and the top 3 terms were associated with cyst morphogenesis, ion transport, and GTPase signal. Following pathway enrichment analyses, a total of 10 significant pathways were enriched; notably, the top 3 pathways were cholinergic synapses, glutamatergic synapses, and oxytocin signaling pathways. Based on PPIN and ego-net analysis, 67 ego genes were found which could completely separate the diseased group from the normal group. The 10 most prominent genes included POLA1, FAM155 B, AMMECR1, THOC2, CCND1, CLDN11, IDS, TST, RBPJ, and GNA11. SVM analysis confirmed that this grouping approach was precise. Conclusions. This research provides useful data to further explore novel genes and pathways as therapeutic targets for parathyroid tumors.

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RBPJ and MAML3: Potential Therapeutic Targets for Small Cell Lung Cancer

Abstract: These results suggest that RBPJ and MAML3 could be new therapeutic targets for SCLC, however, chemosensitivity may be reduced in combinational use with other chemo-therapeutic agents.

Cited by 17 publications

References 4 publications

FOXE1 supports the tumor promotion of Gli2 on papillary thyroid carcinoma by the Wnt/β‐catenin pathway

FOXE1 supports the tumor promotion of Gli2 on papillary thyroid carcinoma by the Wnt/β‐catenin pathway

Single-cell transcriptomics dissects the transcriptome alterations of hematopoietic stem cells in myelodysplastic neoplasms

Genomic Analysis of Abnormal DNAM Methylation in Parathyroid Tumors

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