WiNTRLINC1/ASCL2/c-Myc Axis Characteristics of Colon Cancer with Differentiated Histology at Young Onset and Essential for Cell Viability

Yokota, Kazuko; Tanaka, Yôko; Harada, Hiroki; Kaida, Takeshi; Nakamoto, Syuji; Soeno, Takafumi; Fujiyama, Yoshiki; Yokota, Mitsuo; Kojo, Ken; Miura, Hirohisa; Yamanashi, Takahiro; Sato, Takeo; Nakamura, Takatoshi; Watanabe, Masahiko; Yamashita, Keishi

doi:10.1245/s10434-019-07780-3

Cited by 8 publications

(4 citation statements)

References 35 publications

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“…Therefore, cancer in elderly individuals also exhibits slower growth than that in young individuals, as their bodies already experience a slower rate of cell development [ 43 , 49 ]. Yamashita et al also identified that the WiNTRLINC1/ASCL2/c-Myc axis, which is important for the viability of colon cancer cells, is unique to early-onset differentiated colon cancer [ 50 ]. The malignancy of a tumor is directly proportional to the number of proliferative cells in the cancer tissue.…”

Section: Discussionmentioning

confidence: 99%

A novel nomogram based on cell cycle-related genes for predicting overall survival in early-onset colorectal cancer

et al. 2023

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Background Although the incidence of late-onset colorectal cancer (LOCRC) has decreased, the incidence of early-onset colorectal cancer (EOCRC) is still rising dramatically. Heterogeneity in the genomic, biological, and clinicopathological characteristics between EOCRC and LOCRC has been revealed. Therefore, the previous prognostic models based on the total CRC patient population might not be suitable for EOCRC patients. Here, we constructed a prognostic classifier to enhance the precision of individualized treatment and management of EOCRC patients. Methods EOCRC expression data were downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The regulatory pathways were explored by gene set enrichment analysis (GSEA). The prognostic model was developed by univariate Cox-LASSO-multivariate Cox regression analyses of GEO samples. TCGA samples were used to verify the model. The expression and mutation profiles and immune landscape of the high-risk and low-risk cohorts were analyzed and compared. Finally, the expression and prognostic value of the model genes were verified by immunohistochemistry and qRT‒PCR analysis. Results The cell cycle was identified as the most significantly enriched oncological signature of EOCRC. Then, a 4-gene prognostic signature comprising MCM2, INHBA, CGREF1, and KLF9 was constructed. The risk score was an independent predictor of overall survival. The area under the curve values of the classifier for 1-, 3-, and 5-year survival were 0.856, 0.893, and 0.826, respectively, in the training set and 0.749, 0.858, and 0.865, respectively, in the validation set. Impaired DNA damage repair capability (p < 0.05) and frequent PIK3CA mutations (p < 0.05) were found in the high-risk cohort. CD8 T cells (p < 0.05), activated memory CD4 T cells (p < 0.01), and activated dendritic cells (p < 0.05) were clustered in the low-risk group. Finally, we verified the expression of MCM2, INHBA, CGREF1, and KLF9. Their prognostic value was closely related to age. Conclusion In this study, a robust prognostic classifier for EOCRC was established and validated. The findings may provide a reference for individualized treatment and medical decision-making for patients with EOCRC.

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Section: Discussionmentioning

confidence: 99%

A novel nomogram based on cell cycle-related genes for predicting overall survival in early-onset colorectal cancer

et al. 2023

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“…Together with our early reports regarding Ascl2 , one of the stem cell markers of colon cancer [ 34 , 35 ], we herein investigated other well-known stem cell markers such as CD44V and CD133 at mRNA level in primary colon cancer. As a result, stem cell markers of CD44V showed remarkable increase of their expression in primary colon tumor tissues like Ascl2 [ 34 , 35 ], but not associate with aggressive phenotypes of colon cancer at all. These findings suggested that cancer stemness caused by Ascl2 and CD44V does not necessarily represent metastatic potential in clinical samples of the primary tumors.…”

Section: Discussionmentioning

confidence: 99%

Less demand on stem cell marker-positive cancer cells may characterize metastasis of colon cancer

et al. 2023

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Background CD44 and CD133 are stem cell markers in colorectal cancer (CRC). CD44 has distinctive isoforms with different oncological properties like total CD44 (CD44T) and variant CD44 (CD44V). Clinical significance of such markers remains elusive. Methods Sixty colon cancer were examined for CD44T/CD44V and CD133 at mRNA level in a quantitative PCR, and clarified for their association with clinicopathological factors. Results (1) Both CD44T and CD44V showed higher expression in primary colon tumors than in non-cancerous mucosas (p<0.0001), while CD133 was expressed even in non-cancerous mucosa and rather decreased in the tumors (p = 0.048). (2) CD44V expression was significantly associated with CD44T expression (R = 0.62, p<0.0001), while they were not correlated to CD133 at all in the primary tumors. (3) CD44V/CD44T expressions were significantly higher in right colon cancer than in left colon cancer (p = 0.035/p = 0.012, respectively), while CD133 expression were not (p = 0.20). (4) In primary tumors, unexpectedly, CD44V/CD44T/CD133 mRNA expressions were not correlated with aggressive phenotypes, but CD44V/CD44T rather significantly with less aggressive lymph node metastasis/distant metastasis (p = 0.040/p = 0.039, respectively). Moreover, both CD44V and CD133 expressions were significantly decreased in liver metastasis as compared to primary tumors (p = 0.0005 and p = 0.0006, respectively). Conclusion Our transcript expression analysis of cancer stem cell markers did not conclude that their expression could represent aggressive phenotypes of primary and metastatic tumors, and rather represented less demand on stem cell marker-positive cancer cells.

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“…We demonstrate that lncRNA HDAC4-AS1 is a regulatory target responding to oxygen concentration in RPE cells. Previous studies suggested that several types of lncRNAs could be enriched in promoters of nearby genes [ 23 , 24 ]. Histone deacetylases (HDACs) play important roles in CNV [ 25 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA histone deacetylase 4 antisense RNA 1 (HDAC4-AS1) inhibits HDAC4 expression in human ARPE-19 cells with hypoxic stress

Pan

Zhao

2021

Bioengineered

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Age-related macular degeneration (AMD) is resulted from choroidal neovascularization (CNV)mediated cicatrization and vision loss. The sustained retinal hypoxia in retinal pigment epithelium (RPE) cells was reported to contribute to CNV. However, the underlying genetic regulatory network of hypoxia response in RPE is not fully understood. In this study, human ARPE-19 RPE cells were cultured under the anoxia for 24 h and later re-oxygenated in normoxia. Then the transcriptome was investigated via high throughput sequencing. We observed that long noncoding RNA (lncRNA) histone deacetylase 4 antisense RNA 1 (HDAC4-AS1) was increased in hypoxic condition compared to normal control and decreased after re-oxygenation addition, while the change of HDAC4 expression was reduced in hypoxic condition compared to normal control and up-regulated after re-oxygenation addition in ARPE-19 cells. Furthermore, HDAC4-AS1 knockdown could suppress the transcription activity of HDAC4 only in hypoxia condition, and fluorescence in situ hybridization and pull down assay indicated that transcripts of HDAC4-AS1 could substantially bind to the promoter of HDAC4 and facilitate the recruitment of HIF-1α. Finally, we also determined the specific regions of HDAC4-AS1 that contribute to the interaction with HIF-1α and the promoter of HDAC4. Taken together, these outcomes declared that HDAC4-AS1 could inhibit HDAC4 expression through regulating HIF-1α in human ARPE-19 cells with hypoxic stress.

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WiNTRLINC1/ASCL2/c-Myc Axis Characteristics of Colon Cancer with Differentiated Histology at Young Onset and Essential for Cell Viability

Cited by 8 publications

References 35 publications

A novel nomogram based on cell cycle-related genes for predicting overall survival in early-onset colorectal cancer

A novel nomogram based on cell cycle-related genes for predicting overall survival in early-onset colorectal cancer

Less demand on stem cell marker-positive cancer cells may characterize metastasis of colon cancer

Long non-coding RNA histone deacetylase 4 antisense RNA 1 (HDAC4-AS1) inhibits HDAC4 expression in human ARPE-19 cells with hypoxic stress

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