Evaluation of MACF1-regulatory non-coding RNA as a potential therapeutic target in Colorectal Cancer

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Rowaida Mohammed Reda M. M Aboushahba ◽  
Fayda Ibrahim Abdel Motaleb ◽  
Ahmed Abdel Aziz Abou-Zeid ◽  
Enas Samir Nabil ◽  
Dalia Abdel-Wahab Mohamed ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Wnt Signaling ◽  
Cell Line ◽  
Signaling Pathway ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Wnt Signaling Pathway ◽  
Control Group ◽  
Potential Therapeutic Target

ABSTRACT Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths world-wide. There is an increasing need for the identification of novel biomarkers/targets for early diagnosis and for the development of novel chemopreventive and therapeutic agents for CRC. Recently, MACF1 gene has emerged as a potential therapeutic target in cancer as it involved in processes critical for tumor cell proliferation, invasion and metastasis. It is suggested that MACF1 may function in cancers through Wnt signaling. MiR-34a is a well-known tumor suppressor miRNA.miR-34a targets MACF1 gene as a part of the wnt signaling pathway. In this study, 40 colonic tissues were collected from CRC patients (20) and control subjects (20). miR-34a-5p was assessed by real time PCR in all study groups. The results showed highly significant decrease (P < 0.01) in miR-34a relative expression in the CRC group (median RQ 0.13) when compared to the benign group (median RQ 5.3) and the healthy control group (median RQ 19.63). miR-34a mimic and inhibitor were transfected in CaCo-2 cell line and proliferation was assessed. The transfection of the cell line with miR-34a mimic decreased cell proliferation. Our study suggests that miR-34a-5p targets MACF1 gene as a part of the wnt signaling pathway leading to the involvement in the molecular mechanisms of CRC development and progression.

The Wnt signaling pathway: a potential therapeutic target against cancer

2019 ◽  
Vol 1443 (1) ◽  
pp. 54-74 ◽  
Author(s):  
Noyel Ghosh ◽  
Uday Hossain ◽  
Ankita Mandal ◽  
Parames C. Sil
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Therapeutic Target ◽  
Wnt Signaling Pathway ◽  
Potential Therapeutic Target

scholarly journals MTA3 regulates malignant progression of colorectal cancer through Wnt signaling pathway

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769502 ◽  
Author(s):  
Taiwei Jiao ◽  
Yue Li ◽  
Tong Gao ◽  
Yining Zhang ◽  
Mingliang Feng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Wnt Signaling ◽  
Cell Line ◽  
Signaling Pathway ◽  
Cell Cycle Progression ◽  
Wnt Signaling Pathway ◽  
Lovo Cell ◽  
Induced Apoptosis ◽  
Cancer Tissues

MTA3 overexpression has been implicated in carcinogenesis. The aim of the present study was to explore the clinical significance and biological roles of MTA3 in human colorectal cancer and colorectal cancer cells. A total of 80 cases of colorectal cancer tissues were examined by immunohistochemistry for MTA3 protein expression. We analyzed the relationship between MTA3 and clinical factors and the results showed that MTA3 was overexpressed in 51.25% (41/80) cancer cases. There was significant associations between MTA3 overexpression and advanced TNM stage (p = 0.0086) and Ki67 index (p = 0.001). We overexpressed MTA3 in LoVo cells and depleted its expression in HCT15 cells. The results showed that MTA3 promoted cancer cell proliferation, invasion, migration, and cell cycle progression, and inhibited 5-fluorouracil-induced apoptosis in LoVo cell line. MTA3 depletion in HCT15 cell line showed the opposite effects. In addition, we found that MTA3 positively regulated cell cycle proteins including cyclin D1 and cyclin E. It also upregulated Bcl2 and downregulated Bax expression. Furthermore, we found that MTA3 could activate Wnt signaling pathway by upregulating Wnt target proteins. Our results demonstrated that MTA3 overexpression contributes to colorectal cancer carcinogenesis, progression, and chemoresistance. MTA3 could serve as a potential therapeutic target in colorectal cancer.

scholarly journals Overexpression of ICAT Inhibits the Progression of Colorectal Cancer by Binding with β-Catenin in the Cytoplasm

2021 ◽  
Vol 20 ◽  
pp. 153303382110412
Author(s):  
Jiancong Hu ◽  
Zihan Wang ◽  
Junxiong Chen ◽  
Zhaoliang Yu ◽  
Jingdan Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Transcriptional Activity ◽  
Wnt Pathway ◽  
Wnt Signaling Pathway ◽  
T Cell Factor

Inhibitor of β-catenin and T-cell factor (ICAT) was first found as a polypeptide that blocks β-catenin–TCF interaction. Abundant evidence has shown that ICAT has different functions in diverse cancers’ progression. Nevertheless, the roles it plays in colorectal cancer (CRC) have not been described. Here, we documented that ICAT expression was higher in CRC tissue than in the adjacent normal tissue and that prognosis was better in high-ICAT expression patients. The overexpression of ICAT inhibited CRC cell proliferation both in vitro and in vivo. Wnt pathway transcriptional activity was suppressed in the CRC cells with ICAT overexpression, where the CCND1 and MYC expression, which occurs downstream of the Wnt signaling pathway, was inhibited. Co-immunoprecipitation experiments showed that ICAT bound with β-catenin in stable overexpression cell lines; immunofluorescence showed the co-localization of ICAT and β-catenin in the cytoplasm. Overall, our study reveals that ICAT inhibits CRC cell proliferation by binding to cytoplasm-located β-catenin, and prevents its translocation, which results in Wnt signaling pathway inactivation. It may provide a scientific foundation for focusing on ICAT in treatments for CRC.

scholarly journals Hypermethylation of NDN promotes cell proliferation by activating the Wnt signaling pathway in colorectal cancer

Oncotarget ◽  
2017 ◽  
Vol 8 (28) ◽  
pp. 46191-46203 ◽  
Author(s):  
Yu-Han Hu ◽  
Qing Chen ◽  
Yan-Xia Lu ◽  
Jian-Ming Zhang ◽  
Chun Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway

scholarly journals DNA methylation mediated RSPO2 to promote follicular development in mammals

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Xiaofeng Zhou ◽  
Yingting He ◽  
Nian Li ◽  
Guofeng Bai ◽  
Xiangchun Pan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Methylation Level ◽  
Molecular Mechanisms ◽  
Cpg Island ◽  
Wnt Signaling Pathway ◽  
Follicular Development ◽  
Expression Level

AbstractIn female mammals, the proliferation, apoptosis, and estradiol-17β (E2) secretion of granulosa cells (GCs) have come to decide the fate of follicles. DNA methylation and RSPO2 gene of Wnt signaling pathway have been reported to involve in the survival of GCs and follicular development. However, the molecular mechanisms for how DNA methylation regulates the expression of RSPO2 and participates in the follicular development are not clear. In this study, we found that the mRNA and protein levels of RSPO2 significantly increased during follicular development, but the DNA methylation level of RSPO2 promoter decreased gradually. Inhibition of DNA methylation or DNMT1 knockdown could decrease the methylation level of CpG island (CGI) in RSPO2 promoter and upregulate the expression level of RSPO2 in porcine GCs. The hypomethylation of −758/−749 and −563/−553 regions in RSPO2 promoter facilitated the occupancy of transcription factor E2F1 and promoted the transcriptional activity of RSPO2. Moreover, RSPO2 promoted the proliferation of GCs with increasing the expression level of PCNA, CDK1, and CCND1 and promoted the E2 secretion of GCs with increasing the expression level of CYP19A1 and HSD17B1 and inhibited the apoptosis of GCs with decreasing the expression level of Caspase3, cleaved Caspase3, cleaved Caspase8, cleaved Caspase9, cleaved PARP, and BAX. In addition, RSPO2 knockdown promoted the apoptosis of GCs, blocked the development of follicles, and delayed the onset of puberty with decreasing the expression level of Wnt signaling pathway-related genes (LGR4 and CTNNB1) in vivo. Taken together, the hypomethylation of −758/−749 and −563/−553 regions in RSPO2 promoter facilitated the occupancy of E2F1 and enhanced the transcription of RSPO2, which further promoted the proliferation and E2 secretion of GCs, inhibited the apoptosis of GCs, and ultimately ameliorated the development of follicles through Wnt signaling pathway. This study will provide useful information for further exploration on DNA-methylation-mediated RSPO2 pathway during follicular development.

scholarly journals Inhibition of Wnt signaling by ICAT, a novel β-catenin-interacting protein

2000 ◽  
Vol 14 (14) ◽  
pp. 1741-1749 ◽  
Author(s):  
Ken-ichi Tago ◽  
Tsutomu Nakamura ◽  
Michiru Nishita ◽  
Junko Hyodo ◽  
Shin-ichi Nagai ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Transcription Factors ◽  
Embryonic Development ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Target Genes ◽  
Wnt Signaling Pathway ◽  
Axis Formation ◽  
Interacting Protein

Wnt signaling has an important role in both embryonic development and tumorigenesis. β-Catenin, a key component of the Wnt signaling pathway, interacts with the TCF/LEF family of transcription factors and activates transcription of Wnt target genes. Here, we identify a novel β-catenin-interacting protein, ICAT, that was found to inhibit the interaction of β-catenin with TCF-4 and represses β-catenin–TCF-4-mediated transactivation. Furthermore, ICAT inhibited Xenopus axis formation by interfering with Wnt signaling. These results suggest that ICAT negatively regulates Wnt signaling via inhibition of the interaction between β-catenin and TCF and is integral in development and cell proliferation.

scholarly journals Expression Profile and Prognostic Value of Wnt Signaling Pathway Molecules in Colorectal Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1331
Author(s):  
Yung-Fu Wu ◽  
Chih-Yang Wang ◽  
Wan-Chun Tang ◽  
Yu-Cheng Lee ◽  
Hoang Dang Khoa Ta ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Messenger Rna ◽  
Wnt Signaling Pathway ◽  
Interaction Network ◽  
Mrna Levels ◽  
Key Factor ◽  
Canonical Wnt ◽  
Upregulated Genes

Colorectal cancer (CRC) is a heterogeneous disease with changes in the genetic and epigenetic levels of various genes. The molecular assessment of CRC is gaining increasing attention, and furthermore, there is an increase in biomarker use for disease prognostication. Therefore, the identification of different gene biomarkers through messenger RNA (mRNA) abundance levels may be useful for capturing the complex effects of CRC. In this study, we demonstrate that the high mRNA levels of 10 upregulated genes (DPEP1, KRT80, FABP6, NKD2, FOXQ1, CEMIP, ETV4, TESC, FUT1, and GAS2) are observed in CRC cell lines and public CRC datasets. Moreover, we find that a high mRNA expression of DPEP1, NKD2, CEMIP, ETV4, TESC, or FUT1 is significantly correlated with a worse prognosis in CRC patients. Further investigation reveals that CTNNB1 is the key factor in the interaction of the canonical Wnt signaling pathway with 10 upregulated CRC-associated genes. In particular, we identify NKD2, FOXQ1, and CEMIP as three CTNNB1-regulated genes. Moreover, individual inhibition of the expression of three CTNNB1-regulated genes can cause the growth inhibition of CRC cells. This study reveals efficient biomarkers for the prognosis of CRC and provides a new molecular interaction network for CRC.

Sign in / Sign up

Export Citation Format

Share Document