The role of JAK/STAT signaling pathway and TNF-α crosstalk in human colorectal cancer

: The development of colorectal cancer (CRC) is a multi-stage process. The inflammation of the colon as in inflammatory bowel disease (IBD) such as ulcerative colitis (UC) or Crohn’s disease (CD) is often regarded as the initial trigger for the development of CRC. Many cytokines such as tumor necrosis factor alpha (TNF-α) and several interleukins (ILs) are known to exert proinflammatory actions, and inflammation initiates or promotes tumorigenesis of various cancers, including CRC through differential regulation of microRNAs (miRNAs/miRs). miRNAs can be oncogenic miRNAs (oncomiRs) or anti-oncomiRs/tumor suppressor miRNAs, and they play key roles during colorectal carcinogenesis. However, the functions and molecular mechanisms of regulation of miRNAs involved in inflammation-associated CRC are still anecdotal and largely unknown. Consolidating the published results and offering perspective solutions to circumvent CRC, the current review is focused on the role of miRNAs and their regulation in the development of CRC. We have also discussed the model systems adapted by researchers to delineate the role of miRNAs in inflammation-associated CRC.

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Role of inflammation in the development of colorectal cancer

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200909092908 ◽

2020 ◽

Vol 20 ◽

Author(s):

Sridhar Muthusami ◽

R. Ileng Kumaran ◽

Kokelavani Nampalli Babu ◽

Sneha Krishnamoorthy ◽

Akash Guruswamy ◽

...

Keyword(s):

Colorectal Cancer ◽

Chronic Inflammation ◽

Interleukin 1 ◽

Cell Types ◽

Model Systems ◽

Cytokine Gene Expression ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Proinflammatory Molecules

: Chronic inflammation can lead to the development of many diseases including cancer. Inflammatory bowel disease (IBD) that includes both ulcerative colitis (UC) and Crohn's disease (CD) are risk factors for the development of colorectal cancer (CRC). Many cytokines produced primarily by the gut immune cells either during or in response to localized inflammation in the colon and rectum are known to stimulate the complex interactions between the different cell types in the gut environment resulting in acute inflammation. Subsequently, chronic inflammation together with genetic and epigenetic changes has been shown to lead to the development and progression of CRC. Various cell types present in the colon such as enterocytes, Paneth cells, goblet cells and macrophages express receptors for inflammatory cytokines and respond to tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6 and other cytokines. Among the several cytokines produced, TNF-α and IL-1β are the key proinflammatory molecules that play critical roles in the development of CRC. The current review is intended to consolidate the published findings to focus on the role of proinflammatory cytokines, namely TNF-α and IL-1β, on inflammation (and the altered immune response) in the gut, to better understand the development of CRC in IBD, using various experimental model systems, preclinical and clinical studies. Moreover, this review also highlights the current therapeutic strategies available (monotherapy and combination therapy), to alleviate the symptoms or treat inflammationassociated CRC by using monoclonal antibodies or aptamers to block proinflammatory molecules, inhibitors of tyrosine kinases in inflammatory signaling cascade, competitive inhibitors of proinflammatory molecules, and the nucleic acid drugs like small activating RNAs (saRNAs) or microRNA (miRNA) mimics to activate tumor suppressor or repress oncogene/proinflammatory cytokine gene expression.

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Role of testosterone in regulating induction of TNF-α in rat spleen via ERK signaling pathway

Steroids ◽

10.1016/j.steroids.2016.03.007 ◽

2016 ◽

Vol 111 ◽

pp. 148-154 ◽

Cited By ~ 8

Author(s):

Chien-Wei Chen ◽

Cai-Yun Jian ◽

Po-Han Lin ◽

Chih-Chieh Chen ◽

Fu-Kong Lieu ◽

...

Keyword(s):

Signaling Pathway ◽

Erk Signaling ◽

Tnf Α

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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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Study on the role of JAK/STAT signaling pathway during chicken spermatogonial stem cells generation based on RNA-Seq

Journal of Integrative Agriculture ◽

10.1016/s2095-3119(14)60938-2 ◽

2015 ◽

Vol 14 (5) ◽

pp. 939-948 ◽

Cited By ~ 5

Author(s):

Lei ZHANG ◽

Qi-sheng ZUO ◽

Dong LI ◽

Chao LIAN ◽

Kamel E Ahmed ◽

...

Keyword(s):

Stem Cells ◽

Signaling Pathway ◽

Spermatogonial Stem Cells ◽

Rna Seq ◽

Stat Signaling

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Apoptosis effect of Aegiceras corniculatum on human colorectal cancer via activation of FoxO signaling pathway

Food and Chemical Toxicology ◽

10.1016/j.fct.2019.110861 ◽

2019 ◽

Vol 134 ◽

pp. 110861 ◽

Cited By ~ 2

Author(s):

Hua Luo ◽

Erwei Hao ◽

Dechao Tan ◽

Wei Wei ◽

Jinling Xie ◽

...

Keyword(s):

Colorectal Cancer ◽

Signaling Pathway ◽

Human Colorectal Cancer ◽

Aegiceras Corniculatum ◽

Foxo Signaling Pathway

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Stem Cell-Derived Exosomes Prevent Aging-Induced Cardiac Dysfunction through a Novel Exosome/lncRNA MALAT1/NF-κB/TNF-α Signaling Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/9739258 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14 ◽

Cited By ~ 15

Author(s):

Bao Zhu ◽

Lulu Zhang ◽

Chun Liang ◽

Bin Liu ◽

Xiangbin Pan ◽

...

Keyword(s):

Stem Cell ◽

Signaling Pathway ◽

Cardiac Dysfunction ◽

Human Umbilical Cord ◽

Beneficial Effects ◽

Age Related ◽

Lncrna Malat1 ◽

Tnf Α ◽

Heart Functions

Aging is a risk factor for cardiovascular disease, and there is no effective therapeutic approach to alleviate this condition. NF-κB and TNF-α have been implicated in the activation of the aging process, but the signaling molecules responsible for the inactivation of NF-κB and TNF-α remain unknown. Exosomes have been reported to improve heart functions by releasing miRNA. Recent studies suggest that lncRNAs are more tissue-specific and developmental stage-specific compared to miRNA. However, the role of lncRNA in exosome-mediated cardiac repair has not been explored. In the present study, we focused on metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), which is an lncRNA associated with cell senescence. We discovered that human umbilical cord mesenchymal stem cell- (UMSC-) derived exosomes prevent aging-induced cardiac dysfunction. Silencer RNA against lncRNA MALAT1 blocked the beneficial effects of exosomes. In summary, we discovered that UMSC-derived exosomes prevent aging-induced cardiac dysfunction by releasing novel lncRNA MALAT1, which in turn inhibits the NF-κB/TNF-α signaling pathway. These findings will lead to the development of therapies that delay aging and progression of age-related diseases.

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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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