XB130 enhances invasion and migration of human colorectal cancer cells by promoting epithelial-mesenchymal transition

Shen, Jiancheng; Jin, Chang'e; Liu, Yonglin; Rao, Heping; Liu, Jinrong; Li, Jie

doi:10.3892/mmr.2017.7279

Cited by 10 publications

(5 citation statements)

References 23 publications

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“…These findings are consistent with previous studies on XB130 in a variety of cancers, e.g., thyroid tumor [19,31], prostate cancer [15], lung cancer [17], gastric cancer [32], breast cancer PLOS ONE [33], colorectal cancer [34], hepatocellular carcinoma [35], and skin tumor [24]. XB130 has been suggested to play significant roles in cancer progression through PI3K/Akt signaling pathway, leading to an increase in tumorigenic properties, including cell growth, migration, invasion and epithelial-mesenchymal transition (EMT) process [17,31,[35][36][37].…”

Section: Discussionsupporting

confidence: 92%

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Section: Discussionsupporting

confidence: 92%

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“…To date, the function of XB130 protein has been well elucidated, but there has been limited research on the regulation of its expression (1)(2)(3)(4)(5)(6)10,19,(23)(24)(25)(26)(27). The present study indicated that the insertion of the 661-795 or 792-989 3'-UTR fragments into the psiCHECK-2 vector increased the luciferase activity of the reporter gene, compared with the Ctrl group.…”

Section: Discussionmentioning

confidence: 50%

The 3'‑untranslated region of XB130 regulates its mRNA stability and translational efficiency in non‑small cell lung cancer cells

Wang,

Liu,

Gou

et al. 2023

Oncol Lett

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Silencing XB130 inhibits cell proliferation and epithelial-mesenchymal transition in non-small cell lung cancer (NSCLC), suggesting that downregulating XB130 expression may impede NSCLC progression. However, the molecular mechanism underlying the regulation of XB130 expression remains unclear. In the present study, the role of the 3'-untranslated region (3'-UTR) in the regulation of XB130 expression was investigated. Recombinant psiCHECK-2 vectors with wild-type, truncated, or mutant XB130 3'-UTR were constructed, and the effects of these insertions on reporter gene expression were examined using a dual-luciferase reporter assay and reverse transcription-quantitative PCR. Additionally, candidate proteins that regulated XB130 expression by binding to critical regions of the XB130 3'-UTR were screened for using an RNA pull-down assay, followed by mass spectrometry and western blotting. The results revealed that insertion of the entire XB130 3'-UTR (1,218 bp) enhanced reporter gene expression. Positive regulatory elements were primarily found in nucleotides 113-989 of the 3'-UTR, while negative regulatory elements were found in the 1-112 and 990-1,218 regions of the 3'-UTR. Deletion analyses identified nucleotides 113-230 and 503-660 of the 3'-UTR as two major fragments that likely promote XB130 expression by increasing mRNA stability and translation rate. Additionally, a U-rich element in the 970-1,053 region of the 3'-UTR was identified as a negative regulatory element that inhibited XB130 expression by suppressing translation. Furthermore, seven candidate proteins that potentially regulated XB130 expression by binding to the 113-230, 503-660, and 970-1,053 regions of the 3'-UTR were identified, shedding light on the regulatory mechanism of XB130 expression. Collectively, these results suggested that complex sequence integrations in the mRNA 3'-UTR variably affected XB130 expression in NSCLC cells.

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“…FOXO3 inhibits AGS cell growth by promoting Beclin1-medicated autophagy and inhibiting p62 protein expression in an acidic microenvironment [55]. XB130 promotes human colorectal cancer cell migration and invasion by enhancing phosphorylation of FOXO3a and epithelial-mesenchymal transition [56]. DFOG, a novel synthetic genistein analogue, decreases the level of phosphorylated FOXO3a to inhibit the ovarian cancer sphere-forming cell self-renewal activity [57].…”

Section: Discussionmentioning

confidence: 99%

A Feedback Loop Formed by ATG7/Autophagy, FOXO3a/miR-145 and PD-L1 Regulates Stem-like Properties and Invasion in Human Bladder Cancer

Zhu

Luo

et al. 2019

Cancers

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Programmed cell death protein 1 (PD-1) and its ligand PD-L1 blockade have been identified to target immune checkpoints to treat human cancers with durable clinical benefit. Several studies reveal that the response to PD-1-PD-L1 blockade might correlate with PD-L1 expression levels in tumor cells. However, the mechanistic pathways that regulate PD-L1 protein expression are not understood. Here, we reported that PD-L1 protein is regulated by ATG7-autophagy with an ATG7-initiated positive feedback loop in bladder cancer (BC). Mechanistic studies revealed that ATG7 overexpression elevates PD-L1 protein level mainly through promoting autophagy-mediated degradation of FOXO3a, thereby inhibiting its initiated miR-145 transcription. The lower expression of miR-145 increases pd-l1 mRNA stability due to the reduction of its direct binding to 3′-UTR of pd-l1 mRNA, in turn leading to increasing in pd-l1 mRNA stability and expression, and finally enhancing stem-like property and invasion of BC cells. Notably, overexpression of PD-L1 in ATG7 knockdown cells can reverse the defect of autophagy activation, FOXO3A degradation, and miR-145 transcription attenuation. Collectively, our results revealed a positive feedback loop to promoting PD-L1 expression in human BC cells. Our study uncovers a novel molecular mechanism for regulating pd-l1 mRNA stability and expression via ATG7/autophagy/FOXO3A/miR-145 axis and reveals the potential for using combination treatment with autophagy inhibitors and PD-1/PD-L1 immune checkpoint blockade to enhance therapeutic efficacy for human BCs.

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XB130 enhances invasion and migration of human colorectal cancer cells by promoting epithelial-mesenchymal transition

Cited by 10 publications

References 23 publications

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The 3'‑untranslated region of XB130 regulates its mRNA stability and translational efficiency in non‑small cell lung cancer cells

A Feedback Loop Formed by ATG7/Autophagy, FOXO3a/miR-145 and PD-L1 Regulates Stem-like Properties and Invasion in Human Bladder Cancer

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