The essential role of TAp73 in bortezomib-induced apoptosis in p53-deficient colorectal cancer cells

Objectives: This study aimed to investigate the potential function of miR-214 in the apoptosis induction by targeting p53 in human colorectal cancer cells (CRC) in combination with doxorubicin (DOX). Methods: miR-214 mimics were transfected to HT-29 CRC cells. Following that, the transfected cells were treated with DOX. Cell viability, apoptosis, and migration were evaluated by MTT, flow cytometry, and scratch-wound motility assays, respectively. Furthermore, the expression level of miR-214 and p53 was evaluated by qRT-PCR. Results: miR-214 transfection significantly inhibited the cell proliferation rate (P<0.05), induced apoptosis (P<0.05), and harnessed migration (P<0.05) in the HT-29 cells after 48 h. Furthermore, more effectiveness was observed in combination with DOX. Additionally, miR-214 transfection led to a reduction in p53 expression offering that it might be a potential target for miR-214. Conclusion: In conclusion, miR-214 sensitizes HT-29 cells to doxorubicin by targeting p53 indicating the significant role of this miRNA in colorectal cancer chemotherapy.

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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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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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