IRX5 promotes colorectal cancer metastasis by negatively regulating the core components of the RHOA pathway

Zhu, Quan; Wu, Yiqi; Yang, Mei; Wang, Zhen; Zhang, Hailing; Jiang, Xinying; Chen, Meng; Jin, Tianyu; Wang, Ting

doi:10.1002/mc.23098

Cited by 22 publications

(17 citation statements)

References 44 publications

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“…IRX5 alone has also been reported to be an oncogenic gene in hepatocellular carcinoma, colorectal cancer, prostate cancer, and non-small cell lung cancer by regulating cancer cell cycle and apoptosis (Myrthue et al, 2008;Zhang D.L. et al, 2018;Zhu et al, 2019Zhu et al, , 2020. Although there is no direct evidence that FTO SNPs are associated with cancer by affecting the expression of adjacent genes, we cannot rule it out as a possibility.…”

Section: Controversy On the Mechanism Of Association Between Fto Riskmentioning

confidence: 93%

FTO – A Common Genetic Basis for Obesity and Cancer

et al. 2020

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In recent years, the prevalence of obesity and cancer have been rising. Since this poses a serious threat to human health, the relationship between the two has attracted much attention. This study examined whether fat mass and obesity-associated ( FTO ) genes are linked, taking into account a Genome-wide Association Study (GWAS) that revealed multiple single nucleotide polymorphism sites (SNPs) of the FTO gene, indicating an association between obesity and cancer in different populations. FTO proteins have been proved to participate in adipogenesis and tumorigenesis with post-transcriptional regulation of downstream molecular expression or through the target of the mammalian target protein rapamycin (mTOR). FTO inhibitors have also been found to share anti-obesity and anti-cancer effects in vivo . In this review, we comprehensively discuss the correlation between obesity and cancer by measuring FTO gene polymorphism, as well as the molecular mechanism involved in these diseases, emphasizing FTO as the common genetic basis of obesity and cancer.

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Section: Controversy On the Mechanism Of Association Between Fto Riskmentioning

confidence: 93%

FTO – A Common Genetic Basis for Obesity and Cancer

et al. 2020

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“…The IRX5 is a transcription factor that is closely associated with a variety of malignancies 29,30 . IRX5 can promote the invasion and migration of colorectal cancer cells by inhibiting the RHOA‐ROCK1‐LIMK1 axis 31 . IRX5 expression has been shown to be positively correlated with OS in smokers and negatively correlated with OS in non‐smokers with LUAD 32 .…”

Section: Discussionmentioning

confidence: 99%

Systematic profiling of invasion‐related gene signature predicts prognostic features of lung adenocarcinoma

Tong

Song

et al. 2021

J Cellular Molecular Medi

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Due to the high heterogeneity of lung adenocarcinoma (LUAD), molecular subtype based on gene expression profiles is of great significance for diagnosis and prognosis prediction in patients with LUAD. Invasion‐related genes were obtained from the CancerSEA database, and LUAD expression profiles were downloaded from The Cancer Genome Atlas. The ConsensusClusterPlus was used to obtain molecular subtypes based on invasion‐related genes. The limma software package was used to identify differentially expressed genes (DEGs). A multi‐gene risk model was constructed by Lasso‐Cox analysis. A nomogram was also constructed based on risk scores and meaningful clinical features. 3 subtypes (C1, C2 and C3) based on the expression of 97 invasion‐related genes were obtained. C3 had the worst prognosis. A total of 669 DEGs were identified among the subtypes. Pathway enrichment analysis results showed that the DEGs were mainly enriched in the cell cycle, DNA replication, the p53 signalling pathway and other tumour‐related pathways. A 5‐gene signature (KRT6A, MELTF, IRX5, MS4A1 and CRTAC1) was identified by using Lasso‐Cox analysis. The training, validation and external independent cohorts proved that the model was robust and had better prediction ability than other lung cancer models. The gene expression results showed that the expression levels of MS4A1 and KRT6A in tumour tissues were higher than in normal tissues, while CRTAC1 expression in tumour tissues was lower than in normal tissues. The 5‐gene signature prognostic stratification system based on invasion‐related genes could be used to assess prognostic risk in patients with LUAD.

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“…Recently, RHOA is frequently reported as an oncogenic gene implicating in the initiation and progression of malignant tumors via exacerbating cell migration and invasion [6,8,19,20]. RHOA is widespreadly overexpressed in prostate cancer, cervical cancer and colorectal cancer, and associated with cancer metastasis [21][22][23].…”

Section: Discussionmentioning

confidence: 99%

miR-154-3p and miR-487-3p synergistically modulate RHOA signaling in the carcinogenesis of thyroid cancer

et al. 2020

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Correspondence: Ning An (anning gpch@tom.com) Background: miRs family members are often thought to have extensively overlapping targets and synergistically to modulate target gene expression via post-transcriptional repression. The present study was to determine whether miR-154-3p and miR-487-3p synergistically collaborated to regulate RHOA signaling in the carcinogenesis of thyroid cancer. Materials and methods: Candidate miRs were filtrated using miR microarray assays. Gene and protein expression levels were analyzed using RT-qPCR and Western blotting, respectively. Cell growth was evaluated using CCK8 assays and nude-mouse transplanted tumor experiments. Cell apoptosis was detected using Annexin V-FITC double staining. Results: miR-154-3p and miR-487-3p were significantly decreased in 63 thyroid cancer tissues and cell lines compared with those in paired non-tumor tissues and normal thyroid follicular epithelial cells. Low expression levels of miR-154-3p and miR-487-3p significantly correlated with tumor size, TNM stage, histological grade, lymph node metastasis and shorter overall survival in patients with thyroid cancer. Furthermore, the protein expression of RHOA was significantly inversely correlated with miR-154-3p (r = −0.404; P = 0.001) and miR-487-3p (r = −0.456; P < 0.001) expression in thyroid cancer tissues. We experimentally validated that miR-154-3p and miR-487-3p synergistically blocked thyroid cancer cell growth in vitro and in vivo. However, the anti-proliferative and pro-apoptotic activities of miR-154-3p/487-3p were neutralized by RHOA overexpressed vectors. Conclusions: Our present findings expounded a novel signal cascade employing miR-154-3p/487-3p and RHOA to fine-tune thyroid cancer cell proliferation and apoptosis. We corroborated that suppression of RHOA by miR-154-3p/487-3p may be a valuable therapeutic target for impeding thyroid cancer progression.Ras homolog family member A (RHOA) as a representative protein of RHO subfamily primarily participates in actin cytoskeleton rearrangement, which is implicated in various physiological functions, including cell proliferation, differentiation, migration, polarity and gene transcription [6]. Rho-associated protein kinase (ROCK) is a downstream effector of RHOA and has the ability to modulate cytoskeleton dynamics [6]. Over-activation of RHOA/ROCK signaling pathway may be associated with a decrease in cell-cell junctions and a promotion of cell motility [7]. Previous studies have validated that high expression of RHOA and ROCK is frequently reported in various cancer-types, such as breast cancer, ovarian cancer and colon cancer [6,8,9]. In thyroid cancer, RHOA/ROCK signaling has a profound stimulative impact to facilitate the invasiveness of anaplastic thyroid cancer cells [10]. microRNAs (miRs) are a class of non-coding RNAs and have widely been elaborated in the pathogenesis of various diseases, including carcinogenesis [11]. miRs function as post-transcriptional regulators to repress target genes translation via binding with their 3 -un...

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IRX5 promotes colorectal cancer metastasis by negatively regulating the core components of the RHOA pathway

Cited by 22 publications

References 44 publications

FTO – A Common Genetic Basis for Obesity and Cancer

FTO – A Common Genetic Basis for Obesity and Cancer

Systematic profiling of invasion‐related gene signature predicts prognostic features of lung adenocarcinoma

miR-154-3p and miR-487-3p synergistically modulate RHOA signaling in the carcinogenesis of thyroid cancer

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