Remarkably reduced expression of FoxO3a in metaplastic colorectum, primary colorectal cancer and liver metastasis

He, Leya; Wei, Xin; Du, Lixin; Lü, Ling; Xu, Feng; Jiang, Min; Li, Chuan; Tao, Deding; Chen, Quan; Hu, Junbo; Gong, Jianping

doi:10.1007/s11596-013-1098-7

Cited by 11 publications

(5 citation statements)

References 16 publications

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“…Although expression levels were noted to differ between AA vs. CA tumors, this decreased expression was not statistically significant. These immunohistochemical results support a recent report of decreased FOXO3a (39) expression in CRC, and suggest that miR-182 levels may contribute to the regulation of FOXO1 and FOXO3a expression. The concept that increased miR-182 levels in AA compared to CA levels may contribute to increased AA colon cancer mortality is further supported by a recent report linking miR-182 to reduced colon cancer survival and increased liver metastases (40).…”

Section: Discussionsupporting

confidence: 90%

Differential expression of miRNAs in colon cancer between African and Caucasian Americans: Implications for cancer racial health disparities

Ouyang

et al. 2014

International Journal of Oncology

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Colorectal cancer (CRC) incidence and mortality are higher in African Americans (AAs) than in Caucasian Americans (CAs) and microRNAs (miRNAs) have been found to be dysregulated in colonic and other neoplasias. The aim of this exploratory study was to identify candidate miRNAs that could contribute to potential biological differences between AA and CA colon cancers. Total RNA was isolated from tumor and paired adjacent normal colon tissue from 30 AA and 31 CA colon cancer patients archived at Stony Brook University (SBU) and Washington University (WU)-St. Louis Medical Center. miRNA profiles were determined by probing human genome-wide miRNA arrays with RNA isolated from each sample. Using repeated measures analysis of variance (RANOVA), miRNAs were selected that exhibited significant (p<0.05) interactions between race and tumor or significant (fold change >1.5, p<0.05) main effects of race and/or tumor. Quantitative polymerase chain reaction (q-PCR) was used to confirm miRNAs identified by microarray analysis. Candidate miRNA targets were analyzed using immunohistochemistry. RANOVA results indicated that miR-182, miR152, miR-204, miR-222 and miR-202 exhibited significant race and tumor main effects. Of these miRNAs, q-PCR analysis confirmed that miR-182 was upregulated in AA vs. CA tumors and exhibited significant race:tumor interaction. Immunohistochemical analysis revealed that the levels of FOXO1 and FOXO3A, two potential miR-182 targets, are reduced in AA tumors. miRNAs may play a role in the differences between AA and CA colon cancer. Specifically, differences in miRNA expression levels of miR-182 may contribute to decreased survival in AA colon cancer patients.

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Section: Discussionsupporting

confidence: 90%

Differential expression of miRNAs in colon cancer between African and Caucasian Americans: Implications for cancer racial health disparities

Ouyang

et al. 2014

International Journal of Oncology

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“…Previous studies have demonstrated a negative association between FoxO3a, and cancer grade and spread. In ovarian cancer, liver cancer, breast cancer and prostate cancer, FoxO3a expression is decreased (8,(21)(22)(23). In addition, the nuclear transport and abnormal cytoplasmic distribution of FoxO3a is associated with poor prognosis of breast cancer (9).…”

Section: Discussionmentioning

confidence: 99%

Forkhead box protein O3 suppresses uveal melanoma development by increasing the expression of Bcl‑2‑like protein 11 and cyclin‑dependent kinase inhibitor 1B

et al. 2017

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Forkhead box protein O3 (FoxO3a) is a forkhead box family transcription factor which serves an important role in a number of biological functions, including tumor growth. A previous study indicated that FoxO3a serves a role in insulin like growth factor‑induced growth, migration and invasion of uveal melanoma (UM) cells; however, whether FoxO3a is associated with the development and formation of UM remains unknown. In the present study, the role of FoxO3a in UM development and formation was investigated by modulating the expression of FoxO3a in a human UM cell line. The results of the present study demonstrated that FoxO3a overexpression in UM cells inhibited cell proliferation and promoted cellular apoptosis, leading to an accumulation of cells at the G1 cell cycle phase. Western blot analysis demonstrated that FoxO3a overexpression increased the transcription and protein expression of Bcl‑2‑like protein 11 and cyclin‑dependent kinase inhibitor 1B, and inhibited cyclin D1 transcription and expression. The opposite effects were observed when FoxO3a was knocked down in UM cells. The results of the present study indicated that FoxO3a may exhibit a negative role in UM development and formation, which is consistent with its role as a tumor suppressor.

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“…Breast cancer, prostate cancer, gliomas, and CRC have all been associated with the dysregulated expression of FOXO3 [12][13][14][15][16]. In metaplastic colorectum, liver metastasis, and primary CRC, loss or reduced expression of FOXO3 has been observed [17].…”

Section: Introductionmentioning

confidence: 99%

Genetic Profile of FOXO3 Single-Nucleotide Polymorphism in Colorectal Cancer Patients

Uroog,

Rahmani,

Alsahli

et al. 2023

Oncology

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Introduction: Colorectal cancer (CRC) heritability is determined by the composite relations between inherited variants and environmental factors. In developing countries like India, the incidence rates of CRC are especially increasing. In this study, we have focused on the distribution of the FOXO3 gene polymorphisms among the patients with colorectal cancer in North India. Methods: A case–control study was conducted on 487 colorectal cancer patients and 487 age-matched controls. We genotyped SNPs rs2253310 and rs4946936 through PCR-Restriction fragment length polymorphism (RFLP) analysis and PCR-single stranded conformation polymorphism (SSCP) procedure followed by sequence detection. Results: A significantly increased risk of CRC was observed for the CC genotype of the rs4946936 polymorphism compared to the TT genotype (p= 0.02; OR= 1.40 CI=1.05-1.87). GT haplotype appeared to be a “risk” haplotype (OR- 1.71, 95%CI= 0.82~2.19), while as other haplotypes CC (OR- 0.83, 95% CI=0.32~1.54]), CT (OR- 0.75, 95%CI= 0.25~1.01) and GC (OR- 0.98, 95%CI= 0.88~1.14) were found to be “protective” for developing colorectal cancer. Conclusion: This study suggests an association of increased risk of CRC with the rs4946936 polymorphism, but not with the rs2253310 polymorphism.

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Remarkably reduced expression of FoxO3a in metaplastic colorectum, primary colorectal cancer and liver metastasis

Cited by 11 publications

References 16 publications

Differential expression of miRNAs in colon cancer between African and Caucasian Americans: Implications for cancer racial health disparities

Differential expression of miRNAs in colon cancer between African and Caucasian Americans: Implications for cancer racial health disparities

Forkhead box protein O3 suppresses uveal melanoma development by increasing the expression of Bcl‑2‑like protein 11 and cyclin‑dependent kinase inhibitor 1B

Genetic Profile of FOXO3 Single-Nucleotide Polymorphism in Colorectal Cancer Patients

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