Supplementary choline attenuates olive oil lipid emulsion‐induced enterocyte apoptosis through suppression of <scp>CELF</scp>1/<scp>AIF</scp> pathway

Yan, Junkai; Zhu, Jie; Gong, Zizhen; Wen, Jie; Xiao, Yongtao; Zhang, Tian; Cai, Wei

doi:10.1111/jcmm.13430

Cited by 12 publications

(11 citation statements)

References 44 publications

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“…RNP-IP assays were performed as previously described (21). Briefly, 2×10 7 cells per sample were collected, and the lysates were used for IP at 4°C overnight in the presence of excess (30 µ g) IP antibodies against MBNL1 (1:50, cat.…”

Section: Methodsmentioning

confidence: 99%

Muscleblind‑like 1 destabilizes Snail mRNA and suppresses the metastasis of colorectal cancer cells via the Snail/E‑cadherin axis

2019

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RNA-binding proteins (RBPs) play a fundamental role in the recurrence and metastasis of colorectal cancer (CRC). In this study, we identified muscleblind-like 1 (MBNL1), an RBP implicated in developmental control, as a robust suppressor of CRC cell metastasis in vitro. By using a scratch assay coupled with time-lapse live cell imaging, our findings revealed that the knockdown of MBNL1 induced epithelial-to-mesenchymal transition (EMT)-like morphological changes in the HCT-116 cells, accompanied by an enhanced cell motility, and by the downregulation of E-cadherin and the upregulation of Snail expression. By contrast, the ectopic overexpression of MBNL1 suppressed EMT, characterized by the upregulation of E-cadherin and the downregulation of Snail expression. Mechanistically, Snail rather than E-cadherin, was identified as a direct downstream target gene of MBNL1. The ectopic the overexpression of MBNL1 markedly enhanced the recruitment of Snail transcripts to processing bodies (P-bodies), leading to the increased degradation of Snail mRNA and consequent translational silencing. Furthermore, the effect of MBNL1 on CRC cell migration was confirmed in additional CRC cell lines. SW480 and HT-29 cells exhibited similar changes in migratory capacity and the expression of Snail/E-cadherin to those observed in HCT-116 cells. On the whole, this study demonstrates that MBNL1 destabilizes Snail transcripts and, in turn, suppresses the EMT of CRC cells through the Snail/E-cadherin axis in vitro. Therefore, this EMT-related MBNL1/Snail/E-cadherin axis may prove to be a novel therapeutic target for CRC metastasis.

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Section: Methodsmentioning

confidence: 99%

Muscleblind‑like 1 destabilizes Snail mRNA and suppresses the metastasis of colorectal cancer cells via the Snail/E‑cadherin axis

2019

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“…1). Although TPN-induced villus atrophy comprises changes in both apoptosis and proliferation, one of our previous studies has identified CELF1/apoptosis inducing factor axis as a key pathway mediating changes in apoptosis (26), and thus this present study aimed to verify an alternative CELF1-associated pathway responsible for changes in proliferation. Interestingly, by using HCT-116 cells as an IEC model in vitro, we found that the expression of CELF1 was not constant, but dynamically altered along with the proliferation process, suggesting that the role of CELF1 in proliferation control may be sort of selfadaptive: proliferation rate may affect CELF1 expression and vice versa.…”

Section: Discussionmentioning

confidence: 97%

“…For assessment of the association of endogenous CELF1 with p53 mRNA, RNP-immunoprecipitation complexes were performed as previously described (26). Briefly, the mucosal content was collected in a 2-ml tube for homogenate using MagNa Lyser (Roche), followed by lysis on ice for 30 min in 500 ml PLB buffer containing a cocktail of RNase inhibitor and protease inhibitor.…”

Section: Ribonucleoprotein-immunoprecipitationmentioning

confidence: 99%

CELF1/p53 axis: a sustained antiproliferative signal leading to villus atrophy under total parenteral nutrition

et al. 2018

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Intestinal villus atrophy is a major complication of total parenteral nutrition (TPN). Our previous study revealed that TPN‐induced villus atrophy is accompanied by elevated expression of CUGBP, Elav‐like family member 1 (CELF1); however, its mechanism of action has not been fully understood. Herein, we report a pivotal role of CELF1/p53 axis, which induces a sustained antiproliferative signal, leading to suppressed proliferation of intestinal epithelial cells (IECs). By using a rat model of TPN, we found synchronous upregulation of CELF1 and p53 in jejunum mucosa, accompanied by a 51% decrease in crypt cell proliferation rate. By using HCT‐116 cells as an IEC model in vitro, we found that the expression of CELF1 altered dynamically in parallel to proliferation rate, suggesting a self‐adaptive expression pattern in IECs in vitro. Furthermore, ectopic overexpression of CELF1 elicited a significant antiproliferative effect in HCT‐116, Caco‐2, and IEC‐6 cells, whereas knockdown of CELF1 elicited a significant proproliferative effect. Moreover, cell‐cycle assay revealed that ectopic overexpression of CELF1 induced sustained G2 arrest and G1 arrest in HCT‐116 and IEC‐6 cells, respectively, which could be abolished by p53 silencing. Mechanistically, polysomal profiling and nascent protein analysis revealed that regulation of p53 by CELF1 was mediated through accelerating its protein translation in polysomes. Taken together, our findings revealed a sustained suppression of IEC proliferation evoked by CELF1/p53 axis, which may be a potential therapeutic target for the treatment of TPN‐induced villus atrophy.—Yan, J.‐K., Zhang, T., Dai, L.‐N., Gu, B.‐L., Zhu, J., Yan, W.‐H., Cai, W., Wang, Y. CELF1/p53 axis: a sustained antiproliferative signal leading to villus atrophy under total parenteral nutrition. FASEB J. 33, 3378–3391 (2019). http://www.fasebj.org

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“…Caco-2 cells (ATCC, USA) were cultured in DMEM containing 10% FBS under standard cell culture conditions as described previously. 23 Cell culture reagents were obtained from Thermo (Shanghai, China). Mouse anti-Occludin and GAPDH were purchased from Santa Cruz (Shanghai, China).…”

Section: Cell Culture and Reagentsmentioning

confidence: 99%

Early downregulation of P‐glycoprotein facilitates bacterial attachment to intestinal epithelial cells and thereby triggers barrier dysfunction in a rodent model of total parenteral nutrition

et al. 2020

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Intestinal barrier dysfunction is a major complication of total parenteral nutrition (TPN). Our preliminary study revealed that intestinal P‐glycoprotein (P‐gp) was significantly downregulated under TPN treatment followed by disruption of barrier function, and thus the significance of early downregulation of P‐gp needs to be addressed. Herein, we report a pivotal role of P‐gp in the development of intestinal barrier dysfunction under TPN. Functional suppression of P‐gp may facilitate bacterial attachment to intestinal epithelial cells (IECs) and thereby induce degradation of tight junctions to trigger barrier dysfunction. By using a rat model of TPN, we found early downregulation of P‐gp function in ileum after 3‐day TPN, followed by disruption of barrier function after 7‐day TPN. By using Escherichia coli (E. coli) k88 and DH5α as type strains, we found significantly increased bacterial attachment to IECs in TPN group compared to sham. By using Caco‐2 cells as an IEC model in vitro, we found that functional suppression of P‐gp remarkably facilitated bacterial attachment to Caco‐2 cells, leading to subsequent disruption of intestinal barrier function. Of note, Occludin was significantly downregulated by bacterial attachment when P‐gp was functionally suppressed. Mechanistically, changes on Occludin were attributed to enhanced protein degradation instead of suppressed protein translation. Despite the half‐life of Occludin protein being unchanged by DH5α treatment alone, it was decreased by about 40% when P‐gp was simultaneously suppressed. Taken together, our findings revealed that early downregulation of intestinal P‐gp under TPN may be a potential therapeutic target to prevent the development of barrier dysfunction.

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Supplementary choline attenuates olive oil lipid emulsion‐induced enterocyte apoptosis through suppression of CELF1/AIF pathway

Cited by 12 publications

References 44 publications

Muscleblind‑like 1 destabilizes Snail mRNA and suppresses the metastasis of colorectal cancer cells via the Snail/E‑cadherin axis

Muscleblind‑like 1 destabilizes Snail mRNA and suppresses the metastasis of colorectal cancer cells via the Snail/E‑cadherin axis

CELF1/p53 axis: a sustained antiproliferative signal leading to villus atrophy under total parenteral nutrition

Early downregulation of P‐glycoprotein facilitates bacterial attachment to intestinal epithelial cells and thereby triggers barrier dysfunction in a rodent model of total parenteral nutrition

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