Targeting hyperactive TGFBR2 for treating MYOCD deficient lung cancer

Zhou, Qian; Chen, Wensheng; Fan, Zhenzhen; Chen, Zhipeng; Liang, Jinxia; Zeng, Guandi; Liu, Lu; Liu, Wanting; Yang, Tong; Cao, Xin; Yu, Biao; Xu, Meng; Chen, Ye-Guang; Chen, Liang

doi:10.7150/thno.59816

Cited by 10 publications

(6 citation statements)

References 51 publications

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“…Interestingly, for other genes near significant locus, although some studies have reported that they influence LMA or adipose muscle in pigs, others have reported that these genes are related to cancer or tumor diseases in human pathology. The myocardin ( MYOCD ) gene locus near the MARC0094338 on SSC 12 is associated with lung cancer [ 44 ], the ARho GTPase activating protein 44 ( ARHGAP44 ) gene is associated with tumors [ 45 ], the ElaC Ribonuclease Z 2 ( ELAC2 ) gene is reported to be associated with prostate cancer [ 46 ], the mitogen-activated protein kinase kinase 4 ( MAP2K4 ) gene is associated with breast cancer [ 47 ], F-Box protein 4 ( FBXO4 ) located near ASGA0072817 on SSC 16 is associated with cancer [ 48 ], and fibrillarin like 1 ( FBLL1 ) located near WU_ 10.2_14_144250775 on SSC 14 is associated with liver cancer [ 49 ]. In addition, the arginyl-TRNA synthetase 1 ( RARS1 ) gene has been shown to be associated with various diseases of the central nervous system [ 50 ], slit guidance ligand 3 ( SLIT3 ) located near ALGA0090878 on SSC16 is associated with the bone loss [ 51 ], and the receptor activator of NF-Kb 3 ( RANK3 ) gene is associated with alcoholic femoral head necrosis [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

“…The MYOCD gene locus near the MARC0094338 on SSC 12 is associated with lung cancer [44], the ARHGAP44 gene is associated with tumors [45], the ELAC2 gene is reported to be associated with prostate cancer [46], the MAP2K4 gene is associated with breast cancer [47], FBXO4 located near ASGA0072817 on SSC 16 is associated with cancer [48], and FBLL1 located near WU_10.2_14_144250775 on SSC 14 is associated…”

Section: A C C E P T E D a R T I C L Ementioning

confidence: 99%

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Genome-wide association study for loin muscle area of commercial crossbred pigs

et al. 2023

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Objective: Loin muscle area (LMA) is an important target trait of pig breeding. This study aimed to identify single nucleotide polymorphisms (SNPs) and genes associated with LMA in the Duroc × (Landrace × Yorkshire) crossbred pigs (DLY) Methods: A genome-wide association study (GWAS) was performed using the Illumina 50K chip to map the genetic marker and genes associated with LMA in 511 DLY pigs (255 boars and 256 sows).Results：After quality control, we detected 35,426 SNPs, including six SNPs significantly associated with LMA in pigs, with MARC0094338 and ASGA0072817 being the two key SNPs responsible for 1.77% and 2.48% of the phenotypic variance of LMA, respectively. Based on previous research, we determined two candidate genes (GHR and OXCT1) that are associated with fat deposition and muscle growth and found further additional genes (MYOCD, ARHGAP44, ELAC2, MAP2K4, FBXO4, FBLL1, RARS1, SLIT3 and RANK3) that are presumed to have an effect on LMA. Conclusion:This study contributes to the identification of the mutation that underlies quantitative trait loci (QTLs) associated with LMA and to future pig breeding programs based on marker-assisted selection. Further studies are needed to elucidate the role of the identified candidate genes in the physiological processes involved in LMA regulation.

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Section: Discussionmentioning

confidence: 99%

Section: A C C E P T E D a R T I C L Ementioning

confidence: 99%

Genome-wide association study for loin muscle area of commercial crossbred pigs

et al. 2023

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“…Furthermore, this lncRNA is associated with autophagy genes and is critical for osteosarcoma progression and the occurrence and development of gastric cancer ( Han et al, 2019 ). In addition, autophagy-related lncRNAs are known to be prognostic indicators of head and neck squamous cell carcinoma ( Zhou et al, 2021 ). Based on the above reports, this lncRNA is associated with cancer initiation and spread, can predict cancer prognosis reasonably and may become a potential molecular target.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel lactate metabolism signatures and molecular subtypes for prognosis in hepatocellular carcinoma

Guan

Pan

Ren

et al. 2022

Front. Cell Dev. Biol.

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Background: Evidence has shown that lactate, an immune signaling molecule, is associated with hepatocellular carcinoma (HCC) progression and immune suppression. Therefore, identifying lactate metabolism-related molecules is a promising therapeutic strategy to inhibit the development of HCC and overcome chemotherapy resistance. Long noncoding RNAs (lncRNAs) are related to tumorigenesis and metastasis. Hence, verifying the molecular subtypes of lncRNAs related to lactate metabolism will play a critical role in managing HCC.Methods: Based on HCC data in The Cancer Genome Atlas (TCGA), lactate metabolic pathway-related genes were enriched by gene collection and enrichment analysis (GSEA). Lactate metabolism-related lncRNAs (LM_lncRNAs) were identified by correlation analysis, HCC molecular subtypes were determined using nonnegative matrix factorization (NMF) clustering, and the response of the three subtypes to chemotherapeutics was further evaluated using the Genomic Tumor Sensitive Cell Line (GDSC) dataset. LM_lncRNAs were examined via Lasso-Cox regression analysis to determine prognosis for patients. A Nomagram plot was used to predict patient survival time.Results: Three molecular subtypes of HCC were identified. The survival rate of patients with C1 subtype was higher than that of those with C2 and C3. Additionally, patients with C3 subtype have higher levels of immune cell infiltration and high expression of genes related to immune checkpoints. The GDSC results indicated that patients with C3 subtypes were more sensitive to chemotherapy drugs such as sorafenib and sunitinib. The prognostic risk assessment model consisted of six risk factors (AC034229.4, AC131009.1, MYOSLID, AC008667.1, AC012073.1, AC068025.1) and two protective factors (LINC00402 and AC103858.1). Based on Kaplan-Meier analysis, low-risk HCC patients had a high survival rate, and the receiver operating characteristic curve (ROC), calibration curve, and C-index confirmed good prediction ability.Conclusion: In this study, the molecular subtyping method and prediction model of lactate metabolism-related lncRNAs (LM_lncRNAs) were constructed for the prognosis of HCC patients. This work demonstrated the potential targets of LM_lncRNAs and provided a novel perspective and therapeutic paradigm for future clinical translation.

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“…The activators of MYOCD include p300. The ERK1/2 based phosphorylation of MYOCD inhibits it [172,173,174].…”

Section: Hand1/2mentioning

confidence: 99%

The benign nature and rare occurrence of cardiac myxoma as a possible consequence of the limited cardiac proliferative/ regenerative potential: a systematic review

Shafi

Siddiqui

Jaffry

2022

Preprint

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Background: Cardiac Myxoma (CM) is a primary tumor of heart. Its origins, why the occurrence of primary cardiac tumors is extremely rare and how it may be related to limited cardiac regenerative potential, these aspects are not yet entirely known. This study investigates the key cardiac genes/TFs and signaling pathways to advance our understanding of these important questions. Methods: Databases including PubMed, MEDLINE, and Google Scholar were searched for published articles without any date restrictions, involving cardiac myxoma, cardiac genes/TFs/signaling pathways and their roles in cardiogenesis, proliferation, differentiation, key interactions and tumorigenesis, with focus on cardiomyocytes. Results: The cardiac genetic landscape is governed by a very tight control between proliferation and differentiation-related genes/TFs/pathways. Cardiac myxoma originates possibly as a consequence of dysregulations in the gene expression of differentiation regulators including Tbx5, GATA4, HAND1/2, MYOCD, HOPX, BMPs. Such dysregulations switch the expression of cardiomyocytes into progenitor-like state in cardiac myxoma development by dysregulating Isl1, Baf60 complex, Wnt, FGF, Notch, Mef2c and others. The Nkx2-5 and MSX2 contribute to both proliferation and differentiation of Cardiac Progenitor Cells (CPCs) may possibly serve roles based on the microenvironment and the direction of cell circuitry in cardiac tumorigenesis. The Nkx2-5 in cardiac myxoma may serve to limit progression of tumorigenesis as it has massive control over the proliferation of CPCs. The cardiac cell type-specific genetic programming plays governing role in controlling the tumorigenesis and regenerative potential. Conclusion: The cardiomyocytes have very limited proliferative and regenerative potential. They survive for long periods of time and tightly maintain the gene expression of differentiation genes such as Tbx5, GATA4 that interact with tumor suppressors (TS) and exert TS like effect. The total effect such gene expression exerts is responsible for the rare occurrence and benign nature of primary cardiac tumors. This prevents the progression of tumorigenesis. But this also limits the regenerative and proliferative potential of cardiomyocytes. Cardiac Myxoma (CM) develops as a consequence of dysregulations in these key genes which revert the cells towards progenitor-like state, hallmark of CM. The CM development in carney complex also signifies the role of TS in cardiac cells.

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Targeting hyperactive TGFBR2 for treating MYOCD deficient lung cancer

Cited by 10 publications

References 51 publications

Genome-wide association study for loin muscle area of commercial crossbred pigs

Genome-wide association study for loin muscle area of commercial crossbred pigs

Identification of novel lactate metabolism signatures and molecular subtypes for prognosis in hepatocellular carcinoma

The benign nature and rare occurrence of cardiac myxoma as a possible consequence of the limited cardiac proliferative/ regenerative potential: a systematic review

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