CDX2 increases SLC7A7 expression and proliferation of pig intestinal epithelial cells

Li, Xiangguang; Xu, Gao-Feng; Zhai, Zhe; Gao, Chun‐qi; Yan, Huichao; Xi, Qianyun; Guan, Wutai; Wang, Songbo; Wang, Xiu-Qi

doi:10.18632/oncotarget.8894

Cited by 8 publications

(9 citation statements)

References 39 publications

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“…For CDX2, an intestine-specific TF with a role in the proliferation of porcine intestinal epithelial cell line one, novel intestinal nutrient transporter genes activated by CDX2 were screened (15). The transcription initiation site of miR-145-5p has been predicted use jaspar software (http://jaspar.genereg.net/).…”

Section: Resultsmentioning

confidence: 99%

RETRACTED: CDX2/mir-145-5p/SENP1 Pathways Affect LNCaP Cells Invasion and Migration

Han

Zou

et al. 2019

Front. Oncol.

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Background/Aims: Recently, rapidly accumulating evidence has shown that microRNAs (miRNAs) are involved in human tumorigenesis, and the dysregulation of miRNAs has been observed in many cancers, including prostate cancer. miR-145-5p, an miRNA with reduced expression in prostate cancer cells, has been shown to have a tumor suppressive role in a variety of tumors. However, its underlying mechanism requires further elucidation. Methods: A lentiviral expression vector for miR-145-5p was constructed and used to establish a stable cell line (LNCaP) expressing miR-145-5p. The cells were cultured normally and divided into the control group (control), negative control group (negative control), and test group (miR-145-5p). Inhibition of proliferation was measured by a WST-8 assay. The early apoptosis rate of cells was detected by flow cytometry. Clone formation ability was detected by a clone formation inhibition test. Cell invasion and migration capacity was detected by a Transwell assay. The relative expression levels of proteins were detected by western blotting. We constructed a nude mouse model of prostate cancer to observe the effect of miR-145-5p on the growth of transplanted tumors. TargetScan bioinformatics software was used to predict target genes regulated by miR-14-5p. ChIPBase was used to predict transcription factors with binding sites in the upstream promoter region of miR-145-5p. Quantitative reverse transcription PCR was used to detect the relative expression level of genes. A bifluorescence-reporter gene vector was constructed to confirm the regulation of target genes by miR-145-5p. We used 5′ rapid amplification of cDNA ends to confirm the transcription start site of miR-145-5p.Chromatin immunoprecipitation technology was used to detect the effect of transcription factors binding to miR-145-5p. Results: The overexpression of miR-145-5p not only inhibited the proliferation, invasion, and migration of LNCaP cells but also promoted their early apoptosis. After overexpressing miR-145-5p, the expression of small ubiquitin-like modifier protein-specific protease 1 (SENP1), and caudal-related homeobox 2 (CDX2) protein was decreased in LNCaP cells. The transcription factor CDX2 bound to the miR-145-5p promoter region and inhibited its transcription. The transcription start site of miR-145-5p was located at a guanine residue 1,408 bp upstream of the stem-loop sequence. Upon overexpression, miR-145-5p could bind to the 3′-untranslated region of SENP1 to inhibit its translation. Conclusion: These results suggested that CDX2 inhibits the expression of miR-145-5p, thereby relieving the inhibitory effect of miR-145-5p on the translation of SENP1 and affecting the invasion and migration of prostate cancer cells.

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Section: Resultsmentioning

confidence: 99%

RETRACTED: CDX2/mir-145-5p/SENP1 Pathways Affect LNCaP Cells Invasion and Migration

Han

Zou

et al. 2019

Front. Oncol.

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“…The control, LGR5 -overexpressing and BMI1 -overexpressing cells were cultured in six-well plates (Corning Inc., Corning, NY, USA) at a density of 1 × 10 5 cells/mL in growth medium for 48 h and collected for real-time PCR analysis as previously described [ 40 ]. The gene-specific primers were designed with Primer 5.0 software (Premier Biosoft International) and are detailed in Table S1 .…”

Section: Methodsmentioning

confidence: 99%

LGR5 and BMI1 Increase Pig Intestinal Epithelial Cell Proliferation by Stimulating WNT/β-Catenin Signaling

Wang

Chen

et al. 2018

IJMS

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Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) and B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI1) are markers of fast-cycling and quiescent intestinal stem cells, respectively. To determine the functions of these proteins in large animals, we investigated their effects on the proliferation of intestinal epithelial cells from pigs. Our results indicated that LGR5 and BMI1 are highly conserved proteins and that the pig proteins have greater homology with the human proteins than do mouse proteins. Overexpression of either LGR5 or BMI1 promoted cell proliferation and WNT/β-catenin signaling in pig intestinal epithelial cells (IPEC-J2). Moreover, the activation of WNT/β-catenin signaling by recombinant human WNT3A protein increased cell proliferation and LGR5 and BMI1 protein levels. Conversely, inhibition of WNT/β-catenin signaling using XAV939 reduced cell proliferation and LGR5 and BMI1 protein levels. This is the first report that LGR5 and BMI1 can increase proliferation of pig intestinal epithelial cells by activating WNT/β-catenin signaling.

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“…However, the functional effects of CDX2 on the proliferation of normal intestinal epithelial cells are diverse. Studies on normal intestinal epithelial cells such as IEC-6 [ 7 ], IPEC-1 [ 8 ], blastocysts [ 9 ], and ISCs [ 10 ] revealed that CDX2 stimulates cell proliferation. In addition, porcine milk-derived exosomes increase CDX2 protein expression and IPEC-J2 cell proliferation simultaneously, suggesting that cell proliferation and CDX2 expression do not conflict [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…Studies on cancer cells, including human colorectal carcinoma cells (HT-29) [ 5 ], human colon adenocarcinoma cells (Caco-2) [ 4 ] and gastric cancer cells (BGC-823) [ 6 ], demonstrated that CDX2 inhibits cell proliferation. However, studies on rat intestinal epithelial cells (IEC-6) [ 7 ], porcine intestinal epithelial cells (IPEC-1) [ 8 ], blastocysts [ 9 ], and mice ISCs [ 10 ] produced opposite results, accompanied by high expression of Heparin-binding epidermal growth factor (EGF) like growth factor and proliferating cell nuclear antigen (PCNA) [ 7 ]. Therefore, it is still unknown how CDX2 plays dual roles in different types of cells.…”

Section: Introductionmentioning

confidence: 99%

CDX2 Stimulates the Proliferation of Porcine Intestinal Epithelial Cells by Activating the mTORC1 and Wnt/β-Catenin Signaling Pathways

Fan

Zhai

et al. 2017

IJMS

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Caudal type homeobox 2 (CDX2) is expressed in intestinal epithelial cells and plays a role in gut development and homeostasis by regulating cell proliferation. However, whether CDX2 cooperates with the mammalian target of rapamycin complex 1 (mTORC1) and Wnt/β-catenin signaling pathways to stimulate cell proliferation remains unknown. The objective of this study was to investigate the effect of CDX2 on the proliferation of porcine jejunum epithelial cells (IPEC-J2) and the correlation between CDX2, the mTORC1 and Wnt/β-catenin signaling pathways. CDX2 overexpression and knockdown cell culture models were established to explore the regulation of CDX2 on both pathways. Pathway-specific antagonists were used to verify the effects. The results showed that CDX2 overexpression increased IPEC-J2 cell proliferation and activated both the mTORC1 and Wnt/β-catenin pathways, and that CDX2 knockdown decreased cell proliferation and inhibited both pathways. Furthermore, the mTORC1 and Wnt/β-catenin pathway-specific antagonist rapamycin and XAV939 (3,5,7,8-tetrahydro-2-[4-(trifluoromethyl)]-4H –thiopyrano[4,3-d]pyrimidin-4-one) both suppressed the proliferation of IPEC-J2 cells overexpressing CDX2, and that the combination of rapamycin and XAV939 had an additive effect. Regardless of whether the cells were treated with rapamycin or XAV939 alone or in combination, both mTORC1 and Wnt/β-catenin pathways were down-regulated, accompanied by a decrease in CDX2 expression. Taken together, our data indicate that CDX2 stimulates porcine intestinal epithelial cell proliferation by activating the mTORC1 and Wnt/β-catenin signaling pathways.

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CDX2 increases SLC7A7 expression and proliferation of pig intestinal epithelial cells

Cited by 8 publications

References 39 publications

RETRACTED: CDX2/mir-145-5p/SENP1 Pathways Affect LNCaP Cells Invasion and Migration

RETRACTED: CDX2/mir-145-5p/SENP1 Pathways Affect LNCaP Cells Invasion and Migration

LGR5 and BMI1 Increase Pig Intestinal Epithelial Cell Proliferation by Stimulating WNT/β-Catenin Signaling

CDX2 Stimulates the Proliferation of Porcine Intestinal Epithelial Cells by Activating the mTORC1 and Wnt/β-Catenin Signaling Pathways

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