YY1 Silencing Induces 5-Fluorouracil-Resistance and BCL2L15 Downregulation in Colorectal Cancer Cells: Diagnostic and Prognostic Relevance

Colorectal cancer (CRC) is characterized by genetic heterogeneity and is often diagnosed at an advanced stage. Therefore, there is a need to identify novel predictive markers. Yin Yang 1 (YY1) is a transcription factor playing a dual role in cancer. The present study aimed to investigate whether YY1 expression levels influence CRC cell response to therapy and to identify the transcriptional targets involved. The diagnostic and prognostic values of YY1 and the identified factor(s) in CRC patients were also explored. Silencing of YY1 increased the resistance to 5-Fluorouracil-induced cytotoxicity in two out of four CRC cells with different genotypes. BCL2L15/Bfk pro-apoptotic factor was found selectively expressed in the responder CRC cells and downregulated upon YY1 knockdown. CRC dataset analyses corroborated a tumor-suppressive role for both YY1 and BCL2L15 whose expressions were inversely correlated with aggressiveness. CRC single-cell sequencing dataset analyses demonstrated higher co-expression levels of both YY1 and BCL2L15 within defined tumor cell clusters. Finally, elevated levels of YY1 and BCL2L15 in CRC patients were associated with larger relapse-free survival. Given their observed anti-cancer role, we propose YY1 and BCL2L15 as candidate diagnostic and prognostic CRC biomarkers.

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Notoginseng enhances anti-cancer effect of 5-fluorouracil on human colorectal cancer cells

Cancer Chemotherapy and Pharmacology ◽

10.1007/s00280-006-0350-2 ◽

2006 ◽

Vol 60 (1) ◽

pp. 69-79 ◽

Cited By ~ 61

Author(s):

Chong-Zhi Wang ◽

Xiaoji Luo ◽

Bin Zhang ◽

Wen-Xin Song ◽

Ming Ni ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Human Colorectal Cancer ◽

Anti Cancer ◽

Colorectal Cancer Cells ◽

Human Colorectal Cancer Cells

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Genome-Wide Scan for Copy Number Alteration Association with Relapse-Free Survival in Colorectal Cancer with Liver Metastasis Patients

Journal of Clinical Medicine ◽

10.3390/jcm7110446 ◽

2018 ◽

Vol 7 (11) ◽

pp. 446 ◽

Cited By ~ 1

Author(s):

Po-Sheng Yang ◽

Hsi-Hsien Hsu ◽

Tzu-Chi Hsu ◽

Ming-Jen Chen ◽

Cin-Di Wang ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastasis ◽

Liver Metastases ◽

Copy Number ◽

Copy Number Alteration ◽

Gene Signature ◽

Comparative Genomic ◽

Relapse Free Survival ◽

Cgh Array ◽

Free Survival

Predicting a patient’s risk of recurrence after the resection of liver metastases from colorectal cancer is critical for evaluating and selecting therapeutic approaches. Clinical and pathologic parameters have shown limited accuracy thus far. Therefore, we combined the clinical status with a genomic approach to stratify relapse-free survival in colorectal cancer liver metastases patients. To identify new molecular and genetic signatures specific to colorectal cancer with liver metastasis (CRCLM) patients, we conducted DNA copy number profiling on a cohort of 21 Taiwanese CRCLM patients using a comparative genomic hybridization (CGH) array. We identified a three-gene signature based on differential copy number alteration between patients with different statuses of (1) recurrence and (2) synchronous metastasis. In relapse hotspot regions, only three genes (S100PBP, CSMD2, and TGFBI) were significantly associated with the synchronous liver metastasis factor. A final set of three genes—S100PBP, CSMD2, TGFBI—significantly predicted relapse-free survival in our cohort (p = 0.04) and another CRCLM cohort (p = 0.02). This three-gene signature is the first genomic signature validated for relapse-free survival in post-hepatectomy CRCLM patients. Our three-gene signature was developed using a whole-genome CGH array and has a good prognostic position for the relapse-free survival of CRCLM patients after hepatectomy.

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Assessment of TRPV4 Channel and Its Role in Colorectal Cancer Cells

Biomedical & Pharmacology Journal ◽

10.13005/bpj/1683 ◽

2019 ◽

Vol 12 (2) ◽

pp. 629-638

Author(s):

N. N. Bahari ◽

S. Y. N. Jamaludin ◽

A. H. Jahidin ◽

M. N. Zahary ◽

A. B. Mohd Hilmi

Keyword(s):

Colorectal Cancer ◽

Cell Cycle ◽

Cell Death ◽

Cancer Cells ◽

Human Colorectal Cancer ◽

Expression Levels ◽

Pharmacological Modulation ◽

Colorectal Cancer Cells ◽

Ht 29

The transient receptor potential vanilloid member 4 (TRPV4) is a non-selective calcium (Ca2+)-permeable channel which is widely expressed in different types of tissues including the lungs, liver, kidneys and salivary gland. TRPV4 has been shown to serve as a cellular sensor where it is involved in processes such as osmoregulation, cell volume regulation and thermoregulation. Emerging evidence suggests that TRPV4 also plays important roles in several aspects of cancer progression. Despite the reported roles of TRPV4 in several forms of cancers, the role of TRPV4 in human colorectal cancer remains largely unexplored. In the present study, we sought to establish the potential role of TRPV4 in colorectal cancer by assessing TRPV4 expression levels and investigating whether TRPV4 pharmacological modulation may alter cell proliferation, cell cycle and cell death in colorectal cancer cells. Quantitative real-time PCR analysis revealed that TRPV4 mRNA levels were significantly lower in HT-29 cells than normal colon CCD-18Co cells. However, TRPV4 mRNA was absent in HCT-116 cells. Pharmacological activation of TRPV4 with GSK1016790A significantly enhanced the proliferation of HT-29 cells while TRPV4 inhibition using RN 1734 decreased their proliferation. Increased proliferation in GSK1016790A-treated HT-29 cells was attenuated by co-treatment with RN 1734. Pharmacological modulation of TRPV4 had no effect on the cell cycle progression but promoted cell death in HT-29 cells. Taken together, these findings suggest differential TRPV4 expression levels in human colorectal cancer cells and that pharmacological modulation of TRPV4 produces distinct effects on the proliferation and induces cell death in HT-29 cells.

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Germline INDELs and CNVs in a cohort of colorectal cancer patients: their characteristics, associations with relapse-free survival time, and potential time-varying effects on the risk of relapse

Cancer Medicine ◽

10.1002/cam4.1074 ◽

2017 ◽

Vol 6 (6) ◽

pp. 1220-1232 ◽

Cited By ~ 5

Author(s):

Salem Werdyani ◽

Yajun Yu ◽

Georgia Skardasi ◽

Jingxiong Xu ◽

Konstantin Shestopaloff ◽

...

Keyword(s):

Colorectal Cancer ◽

Survival Time ◽

Cancer Patients ◽

Time Varying ◽

Relapse Free Survival ◽

Free Survival ◽

Colorectal Cancer Patients ◽

Risk Of Relapse

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Circulating inflammation signature predicts overall survival and relapse-free survival in metastatic colorectal cancer

British Journal of Cancer ◽

10.1038/s41416-018-0360-y ◽

2019 ◽

Vol 120 (3) ◽

pp. 340-345 ◽

Cited By ~ 3

Author(s):

Andreas Varkaris ◽

Anastasia Katsiampoura ◽

Jennifer S. Davis ◽

Neeraj Shah ◽

Michael Lam ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Metastatic Colorectal Cancer ◽

Relapse Free Survival ◽

Free Survival

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Nei Endonuclease VIII-Like1 (NEIL1) Inhibits Apoptosis of Human Colorectal Cancer Cells

BioMed Research International ◽

10.1155/2020/5053975 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Wanjuan Xue ◽

Yongcheng Liu ◽

Ningning Xin ◽

Jiyu Miao ◽

Juan Du ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Human Colon ◽

Caspase 9 ◽

Human Colon Cancer ◽

Expression Levels ◽

Colorectal Cancer Cells ◽

Human Colorectal Cancer Cells

The study is aimed at investigating the role of Nei endonuclease VIII-like1 (NEIL1) in the pathogenesis of colorectal cancer (CRC). The human CRC (HCT116 and SW480) cells were subjected to the siRNA silencing and recombinant plasmid overexpression of NEIL1. Transfection of siNEIL1 significantly inhibited the cell growth. It also increased the Bax expression levels, while it decreased the Bcl-2 expression levels in human CRC cells, leading the Bax/Bcl-2 balance toward apoptosis. Moreover, the apoptosis was promoted through the caspase-9 signaling pathway. One the other hand, high expression of NEIL1 promoted the cell viability and reduced the apoptosis, inducing the balance of Bax/Bcl-2 in the human colon cancer cells to be antiapoptotic. In addition, the caspase-9 signaling pathway inhibited apoptosis, contrary to the results obtained by downregulating NEIL1 expression. Furthermore, NEIL1 was negatively regulated by miR-7-5p, indicating that miR-7-5p inhibited the NEIL1 expression after transcription. Overexpression of miR-7-5p reversed the effects of NEIL1 on these CRC cells. In conclusion, NEIL1 promotes the proliferation of CRC cells, which is regulated negatively by miR-7-5p. These findings suggest that NEIL1 is a potential therapeutic target for CRC.

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