The expression profile and clinicopathological significance of Notch1 in patients with colorectal cancer: a meta-analysis

Li, Ganxiong; Zhou, Zheng; Zhou, Hongrun; Zhao, Lili; Chen, Dongdong; Chen, Hongzhi; Zou, Hong; Yan, Qi; Jia, Wei Hua; Pang, Lijuan

doi:10.2217/fon-2017-0178

Cited by 10 publications

(7 citation statements)

References 34 publications

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“…Previous evidence has demonstrated that activated Notch signaling is maintained throughout CRC tumorigenesis (25). In addition, enhanced levels of Notch-1 have been associated with progression, tumor grade and metastasis (26). Using the miRNA target prediction programs, we found that the 3'-UTRs of Notch-1 mRNAs contain conserved miR-449a binding sites, which are highly conserved among human, mouse, rat, chimpanzee, dog and chicken species (Fig.…”

Section: Mir-449a Inhibits Cac Growth and Invasion By Targetingmentioning

confidence: 77%

MicroRNA‑449a is a potential predictor of colitis‑associated colorectal cancer progression

Feng

Song

et al. 2018

Oncol Rep

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An early diagnosis of colitis‑associated colorectal cancer (CAC) is important for its clinical management. However, it is currently difficult to distinguish the different stages of CAC development. MicroRNA dysregulation is common in human colorectal disorders, however little is known regarding whether miRNA affects tumor progression by regulating inflammation. In the present study, we identified a novel miRNA (miR‑449a), the expression of which was significantly reduced in CAC tissues than in paired adjacent non‑cancerous tissues (ANTs). Notably, the level of miR‑449a was in a markedly decreased pattern during the neoplastic transformation of ulcerative colitis (UC)‑to‑CAC, as demonstrated by both clinical investigations and the experimental mouse model induced by AOM/DSS treatment. In addition, we observed that decreased miR‑449a expression was associated with advanced T or N status, later clinical stage and poor histological differentiation of CAC. Mechanistic studies revealed that miR‑449a inhibited the growth and metastasis of human colon cancer cells by directly binding to the 3'‑UTR of Notch‑1 and thereby, suppressed the activation of the Notch signaling pathway. Therefore, these findings provide strong evidence for the translational potential of miR‑449a in the discrimination of patients with UC that is likely to progress into CAC, from those unlikely to progress, as well as in the prognosis and diagnosis of CAC.

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Section: Mir-449a Inhibits Cac Growth and Invasion By Targetingmentioning

confidence: 77%

MicroRNA‑449a is a potential predictor of colitis‑associated colorectal cancer progression

Feng

Song

et al. 2018

Oncol Rep

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“…Notch is a contributory factor for various cancers. [ 14 ] Notch1 is increased in human breast, [ 15 ] colorectal, [ 16 ] esophageal cancer, [ 17 ] pancreatic, [ 18 ] and prostate cancers. [ 19 ] For instance, miR‐139‐5p sensitizes CRC cells to 5‐fluorouracil by targeting Notch‐1.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA LBX2‐AS1 promotes colorectal cancer progression via binding with PTBP1 and stabilizing KAT2A expression

Zhao

Wang

Lin

et al. 2022

J Biochem & Molecular Tox

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The long noncoding RNAs (lncRNAs) have been investigated in colorectal cancer (CRC). The aim of this study is to identify the biological functions of LBX2-AS1 in CRC. Quantitative real-time polymerase chain reaction was used to examine the expression of LBX2-AS1 in CRC cells. Cell counting kit-8 and colony formation assays were performed to examine cell proliferation. Wound healing and transwell invasion assays were performed to examine the cell migration and invasion. The interaction between PTBP1 and LBX2-AS1 or KAT2A was confirmed by RNA immunoprecipitation. The KAT2A messenger RNA (mRNA) stability was probed using the transcriptional inhibitor Actinomycin D. LBX2-AS1 was significantly increased in CRC tissues and cells. Knockdown of LBX2-AS1 inhibited CRC cell proliferation, migration, and invasion. The notch signaling pathway was activated by LBX2-AS1. LBX2-AS1 enhanced the mRNA stability of the histone acetyltransferase KAT2A by interacting with RNA-binding protein PTBP1. LBX2-AS1 acted as an oncogene in CRC.

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“…Notch 3 is overexpressed in a subset of colorectal cancer patients and induction of Notch 3 overexpression in colorectal cancer xenografts led to increased tumour formation [ 84 ]. A meta-analysis of 13 studies, including 3401 patients, reported a significant association between Notch 1 expression and colorectal cancer samples compared to noncancerous normal tissues, and clinical parameters were indicative of colorectal cancer invasion and metastasis (e.g., lymph node metastasis and depth of tumour infiltration in the surrounding tissue) [ 85 ].…”

Section: Notch In Cancer: An Overviewmentioning

confidence: 99%

Top Notch Targeting Strategies in Cancer: A Detailed Overview of Recent Insights and Current Perspectives

Moore

Annett

McClements

et al. 2020

Cells

103

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Evolutionarily conserved Notch plays a critical role in embryonic development and cellular self-renewal. It has both tumour suppressor and oncogenic activity, the latter of which is widely described. Notch-activating mutations are associated with haematological malignancies and several solid tumours including breast, lung and adenoid cystic carcinoma. Moreover, upregulation of Notch receptors and ligands and aberrant Notch signalling is frequently observed in cancer. It is involved in cancer hallmarks including proliferation, survival, migration, angiogenesis, cancer stem cell renewal, metastasis and drug resistance. It is a key component of cell-to-cell interactions between cancer cells and cells of the tumour microenvironment, such as endothelial cells, immune cells and fibroblasts. Notch displays diverse crosstalk with many other oncogenic signalling pathways, and may drive acquired resistance to targeted therapies as well as resistance to standard chemo/radiation therapy. The past 10 years have seen the emergence of different classes of drugs therapeutically targeting Notch including receptor/ligand antibodies, gamma secretase inhibitors (GSI) and most recently, the development of Notch transcription complex inhibitors. It is an exciting time for Notch research with over 70 cancer clinical trials registered and the first-ever Phase III trial of a Notch GSI, nirogacestat, currently at the recruitment stage.

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The expression profile and clinicopathological significance of Notch1 in patients with colorectal cancer: a meta-analysis

Abstract: Notch1 overexpression in CRC suggested aggressive biological behaviors and thus implying that Notch1 may be a useful biomarker in CRCs.

Cited by 10 publications

References 34 publications

MicroRNA‑449a is a potential predictor of colitis‑associated colorectal cancer progression

MicroRNA‑449a is a potential predictor of colitis‑associated colorectal cancer progression

Long noncoding RNA LBX2‐AS1 promotes colorectal cancer progression via binding with PTBP1 and stabilizing KAT2A expression

Top Notch Targeting Strategies in Cancer: A Detailed Overview of Recent Insights and Current Perspectives

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