Tristetraprolin activation by resveratrol inhibits the proliferation and metastasis of colorectal cancer cells

Post-transcriptional regulation of gene expression plays a key role in cellular proliferation, differentiation, migration, and apoptosis. Increasing evidence suggests dysregulated post-transcriptional gene expression as an important mechanism in the pathogenesis of cancer. The tristetraprolin family of RNA-binding proteins (RBPs), which include Zinc Finger Protein 36 (ZFP36; commonly referred to as tristetraprolin (TTP)), Zinc Finger Protein 36 like 1 (ZFP36L1), and Zinc Finger Protein 36 like 2 (ZFP36L2), play key roles in the post-transcriptional regulation of gene expression. Mechanistically, these proteins function by binding to the AU-rich elements within the 3′-untranslated regions of their target mRNAs and, in turn, increasing mRNA turnover. The TTP family RBPs are emerging as key regulators of multiple biological processes relevant to cancer and are aberrantly expressed in numerous human cancers. The TTP family RBPs have tumor-suppressive properties and are also associated with cancer prognosis, metastasis, and resistance to chemotherapy. Herein, we summarize the various hallmark molecular traits of cancers that are reported to be regulated by the TTP family RBPs. We emphasize the role of the TTP family RBPs in the regulation of trait-associated mRNA targets in relevant cancer types/cell lines. Finally, we highlight the potential of the TTP family RBPs as prognostic indicators and discuss the possibility of targeting these TTP family RBPs for therapeutic benefits.

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“…Resveratrol suppressed the proliferation and invasion/metastasis of colorectal cancer cells by activating TTP [39].…”

Section: Pd-l1mentioning

confidence: 98%

The Tristetraprolin Family of RNA-Binding Proteins in Cancer: Progress and Future Prospects

Saini

Chen

Patial

2020

Cancers

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“…In addition, by suppressing the expression of lin-28 homolog A (Lin28A), TTP can increase the expression of the tumor suppressor microRNA (miRNA) let-7, whose expression is negatively regulated by Lin28A [ 29 , 55 ]. The miRNA let-7 has been implicated in the regulation of gene transcription including high mobility group A2 (HMGA2) [ 56 ].…”

Section: Oncogenes and Tumor Suppressor Genes Subjected To Ttp-medmentioning

confidence: 99%

“…Histone deacetylase (HDAC) inhibitors in colorectal cancer cells induce TTP expression through activation of EGR1, which promote its binding affinity to ARE, and thus, reduce cell growth and angiogenesis [ 118 , 119 ]. Resveratrol, a natural polyphenolic compound present in many plant species, including grapes, peanuts, and berries, inhibits cell growth through TTP upregulation in several cancers, including breast [ 142 ], colorectal [ 29 ] and brain cancer [ 74 ]. Molecular activators of PP2A enhance the anti-inflammatory function of TTP in lung cancer cells, and thus, provide pharmacotherapeutic strategies to chronic inflammation-mediated cancer [ 133 ].…”

Section: Regulation Of Ttp Expression In Normal and Cancer Cellsmentioning

confidence: 99%

Roles of Tristetraprolin in Tumorigenesis

Park

Lee

Kang

2018

IJMS

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Genetic loss or mutations in tumor suppressor genes promote tumorigenesis. The prospective tumor suppressor tristetraprolin (TTP) has been shown to negatively regulate tumorigenesis through destabilizing the messenger RNAs of critical genes implicated in both tumor onset and tumor progression. Regulation of TTP has therefore emerged as an important issue in tumorigenesis. Similar to other tumor suppressors, TTP expression is frequently downregualted in various human cancers, and its low expression is correlated with poor prognosis. Additionally, disruption in the regulation of TTP by various mechanisms results in the inactivation of TTP protein or altered TTP expression. A recent study showing alleviation of Myc-driven lymphomagenesis by the forced expression of TTP has shed light on new therapeutic avenues for cancer prevention and treatment through the restoration of TTP expression. In this review, we summarize key oncogenes subjected to the TTP-mediated mRNA degradation, and discuss how dysregulation of TTP can contribute to tumorigenesis. In addition, the control mechanism underlying TTP expression at the posttranscriptional and posttranslational levels will be discussed.

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“…Accumulating evidence has shown that natural plant compounds (NPCs), such as curcumin, resveratrol and dictamnine, have significant clinical benefits in cancer, such as inhibiting cell proliferation, affecting the cell cycle, and promoting apoptosis and/or autophagy (6)(7)(8). In addition, bioactive natural components extracted from plants have received attention for their inhibition of epithelial-mesenchymal transformation (EMT) through anti-inflammatory, anti-fibrosis or anti-oxidant mechanisms (9).…”

Section: Introductionmentioning

confidence: 99%

Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1‑AKT/ERK‑Snail signaling pathway

et al. 2020

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Cyclovirobuxine D (CVB-D) is an alkaloid, which is mainly derived from Buxus microphylla. It has been reported that CVB-D has positive effects on breast cancer, gastric cancer and other malignant tumors. However, to the best of our knowledge, there are no reports regarding the effects of CVB-D on colorectal cancer (CRC). The purpose of the present study was to determine the anticancer effects of CVB-D and further elucidate its molecular mechanism(s). DLD-1 and LoVo cell lines were selected to evaluate the antitumor effect of CVB-D. Cytotoxicity, viability and proliferation were evaluated by the MTT and colony formation assays. Flow cytometry was used to detect the effects on apoptosis and the cell cycle in CVB-D-treated CRC cells. The migration and invasion abilities of CRC cells were examined by wound healing and Transwell assays. In addition, RNA sequencing, bioinformatics analysis and western blotting were performed to investigate the target of drug action and clarify the molecular mechanisms. A xenograft model was established using nude mice, and ultrasound was employed to assess the preclinical therapeutic effects of CVB-D in vivo. It was identified that CVB-D inhibited the proliferation, migration, stemness, angiogenesis and epithelial-mesenchymal transition of CRC cells, and induced apoptosis and S-phase arrest. In addition, CVB-D significantly inhibited the growth of xenografts. It is notable that CVB-D exerted anticancer effects in CRC cells partly by targeting collagen triple helix repeat containing 1 (CTHRC1), which may be upstream of the AKT and ERK pathways. CVB-D exerted anticancer effects through the CTHRC1-AKT/ERK-Snail signaling pathway. Targeted therapy combining CTHRC1 with CVB-D may offer a promising novel therapeutic approach for CRC treatment.

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Tristetraprolin activation by resveratrol inhibits the proliferation and metastasis of colorectal cancer cells

Cited by 25 publications

References 51 publications

The Tristetraprolin Family of RNA-Binding Proteins in Cancer: Progress and Future Prospects

The Tristetraprolin Family of RNA-Binding Proteins in Cancer: Progress and Future Prospects

Roles of Tristetraprolin in Tumorigenesis

Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1‑AKT/ERK‑Snail signaling pathway

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