Targeting RAS signaling pathway as a potential therapeutic target in the treatment of colorectal cancer

Bahrami, Afsane; Hassanian, Seyed Mahdi; Shahidsales, Soodabeh; Farjami, Zahra; Hasanzadeh, Malihe; Anvari, Kazem; Aledavood, Amir; Maftouh, Mina; Ferns, Gordon A.

doi:10.1002/jcp.25890

Cited by 66 publications

(54 citation statements)

References 60 publications

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“…Ras , the first identified oncogene, is frequently abnormally activated in most cancers, including CRC. Ras activates downstream effector proteins, such as phosphoinositide 3‐kinase (PI3K) and RAF1, to modulate the PI3K–AKT and RAF–MEK–ERK pathways , which influence tumourigenesis, growth, invasiveness, angiogenesis, and resistance to anti‐epidermal growth factor receptor (EGFR) therapy . Here, we determined that circITGA7 could competitively bind to miR‐370‐3p to upregulate NF1 expression and modulate the Ras pathway.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circITGA7 inhibits colorectal cancer growth and metastasis by modulating the Ras pathway and upregulating transcription of its host gene ITGA7

Wang

Zhang

et al. 2018

The Journal of Pathology

214

171

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Circular RNAs (circRNAs) are significantly dysregulated in various cancer types. However, the roles and mechanisms of circRNAs in cancer remain largely unknown. In this study, we demonstrated that a novel circRNA (circITGA7) and its linear host gene ITGA7 are both significantly downregulated in colorectal cancer (CRC) tissues and cell lines. These decreased expression levels correlated with CRC progression. Functional assays demonstrated that ectopic circITGA7 expression suppressed the growth and metastasis of CRC cells in vitro and in vivo. Knockdown of circITGA7 or ITGA7 promoted the proliferation and migration of CRC cells in vitro, and enhanced CRC growth in vivo. Mechanistically, by using RNA-sequencing and KEGG enrichment analysis, we found that circITGA7 is a negative regulator of the Ras signalling pathway, and that ITGA7 is associated with cytokine-related signalling pathways. In addition, circITGA7 binds to miR-370-3p to antagonise its suppression of neurofibromin 1, which is a well-known negative regulator of the Ras pathway. Finally, circITGA7 upregulates the transcription of ITGA7 by suppressing RREB1 via the Ras pathway. In conclusion, our findings indicate a suppressor role of circITGA7 and ITGA7 in CRC, and reveal that circITGA7 inhibits the proliferation and metastasis of CRC cells by suppressing the Ras signalling pathway and promoting the transcription of ITGA7, suggesting that circITGA7 is a potential target for CRC treatment. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Section: Discussionmentioning

confidence: 99%

Circular RNA circITGA7 inhibits colorectal cancer growth and metastasis by modulating the Ras pathway and upregulating transcription of its host gene ITGA7

Wang

Zhang

et al. 2018

The Journal of Pathology

214

171

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“…Upon GPCR activation, heterotrimeric G proteins yield Ga-GTP and Gbg subunits [van Blesen et al, 1995]. The Gbg subunit-regulated effectors transduce RTK phosphorylation, causing to activation of Ras in the MAP kinase signaling pathway [Bahrami et al, 2017].…”

Section: Genes and Variations Associated With Risk Of Hscrmentioning

confidence: 99%

Genetic Background of Hirschsprung Disease: A Bridge Between Basic Science and Clinical Application

Bahrami

Joodi

Moetamani‐Ahmadi

et al. 2017

J of Cellular Biochemistry

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Hirschsprung's disease (HSCR) is a congenital disorder, defined by partial or complete loss of the neuronal ganglion cells in the intestinal tract, which is caused by the failure of neural crest cells to migrate completely during intestinal development during fetal life. HSCR has a multifactorial etiology, and genetic factors play a key role in its pathogenesis; these include mutations within several gene loci. These have been identified by screening candidate genes, or by conducting genome wide association (GWAS) studies. However, only a small portion of them have been proposed as major genetic risk factors for the HSCR. In this review, we focus on those genes that have been identified as either low penetrant or high penetrant variants that determine the risk of Hirschsprung's disease.

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“…Raf is an important mediator of the small G-protein signaling step within the MAPK signaling pathway that is frequently activated in malignant tumors (35). Raf amplification or mutation leads to activation of the ERK signaling pathway, and therefore affects multiple tumor characteristics, including uncontrolled proliferation, evasion from apoptosis, invasion, distant metastasis, angiogenesis and immune evasion (36,37).…”

Section: Discussionmentioning

confidence: 99%

Synergistic antitumor activity of low-dose c-Met tyrosine kinase inhibitor and sorafenib on human non-small cell lung cancer cells

Guo

Zheng

et al. 2018

Oncol Lett

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Targeting RAS signaling pathway as a potential therapeutic target in the treatment of colorectal cancer

Cited by 66 publications

References 60 publications

Circular RNA circITGA7 inhibits colorectal cancer growth and metastasis by modulating the Ras pathway and upregulating transcription of its host gene ITGA7

Circular RNA circITGA7 inhibits colorectal cancer growth and metastasis by modulating the Ras pathway and upregulating transcription of its host gene ITGA7

Genetic Background of Hirschsprung Disease: A Bridge Between Basic Science and Clinical Application

Synergistic antitumor activity of low-dose c-Met tyrosine kinase inhibitor and sorafenib on human non-small cell lung cancer cells

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