Long noncoding RNA AGPG regulates PFKFB3-mediated tumor glycolytic reprogramming

Liu, Jia; Liu, Zexian; Wu, Qi; Lü, Yun; Wong, Chau Wei; Miao, Lei; Wang, Yun; Wang, Zixian; Jin, Ying; He, Ming; Ren, Chao; Wang, De Shen; Chen, Dong Liang; Pu, Heng Ying; Feng, Lin; Li, Bo; Xie, Dan; Zeng, Mu Sheng; Huang, Peng; Lin, Aifu; Lin, Dong; Xu, Rui‐Hua; Ju, Huai-Qiang

doi:10.1038/s41467-020-15112-3

Cited by 136 publications

(136 citation statements)

References 59 publications

Supporting

Mentioning

134

Contrasting

Order By: Relevance

“…8,9 Our recent studies have investigated the roles of metabolic microenvironment reprogramming in promoting gastrointestinal cancer progression. [10][11][12][13] However, the effects of acidic stress on cancer and the underlying mechanisms need further study. Thus, we sought to investigate the effects of the acidic tumor microenvironment on CRC stem cells.…”

Section: Introductionmentioning

confidence: 99%

VDR–SOX2 signaling promotes colorectal cancer stemness and malignancy in an acidic microenvironment

Lin

et al. 2020

Sig Transduct Target Ther

Self Cite

View full text Add to dashboard Cite

The acidic tumor microenvironment provides an energy source driving malignant tumor progression. Adaptation of cells to an acidic environment leads to the emergence of cancer stem cells. The expression of the vitamin D receptor (VDR) is closely related to the initiation and development of colorectal carcinoma (CRC), but its regulatory mechanism in CRC stem cells is still unclear. Our study revealed that acidosis reduced VDR expression by downregulating peroxisome proliferator-activated receptor delta (PPARD) expression. Overexpression of VDR effectively suppressed the stemness and oxaliplatin resistance of cells in acidosis. The nuclear export signal in VDR was sensitive to acidosis, and VDR was exported from the nucleus. Chromatin immunoprecipitation (ChIP) and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) analyses showed that VDR transcriptionally repressed SRY-box 2 (SOX2) by binding to the vitamin D response elements in the promoter of SOX2, impairing tumor growth and drug resistance. We demonstrated that a change in the acidic microenvironment combined with overexpression of VDR substantially restricted the occurrence and development of CRC in vivo. These findings reveal a new mechanism by which acidosis could affect the stemness of CRC cells by regulating the expression of SOX2 and show that abnormal VDR expression leads to ineffective activation of vitamin D signaling, resulting in a lack of efficacy of vitamin D in antineoplastic process.

show abstract

Section: Introductionmentioning

confidence: 99%

VDR–SOX2 signaling promotes colorectal cancer stemness and malignancy in an acidic microenvironment

Lin

et al. 2020

Sig Transduct Target Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…ASOs used in vivo with the same sequences were chemically modified by RiboBio (Guangzhou, China). The modifications were described previously 20 , 21 .…”

Section: Methodsmentioning

confidence: 99%

The C/D box small nucleolar RNA SNORD52 regulated by Upf1 facilitates Hepatocarcinogenesis by stabilizing CDK1

Li¹,

Wu²,

Liu³

et al. 2020

Theranostics

View full text Add to dashboard Cite

Rationale: Understanding the roles of small nucleolar RNAs (snoRNAs) in hepatocarcinogenesis will provide new avenues to identify diagnostic and therapeutic targets for hepatocellular carcinoma (HCC). Our previous research confirmed the tumor-suppressive effect of Up-frameshift 1 (Upf1) in HCC. Herein, we examined the expression profiles of snoRNAs regulated by Upf1 in hepatoma cells. Methods: We examined the expression profiles of snoRNAs regulated by Upf1 in hepatoma cells using RNA-sequencing analysis and then investigated the expression and significance of SNORD52 in HCC tissue and different cell lines. The protumorigenic effects of SNORD52 on HCC cells were confirmed both in vitro and in vivo by gain-of-function and loss-of-function assays. RNA pull-down assays and mass spectrometry were used to identify the RNA-binding protein that binds to SNORD52. Results: Many snoRNAs were identified; one of which, the human C/D box small nucleolar RNA SNORD52, was upregulated in HCC tissues and negatively correlated with Upf1 expression, and patients with higher SNORD52 expression had a poor clinical prognosis. SNORD52 promoted HCC tumorigenesis both in vitro and in vivo . Mechanistically, KEGG analysis showed that SNORD52 upregulated a series of cell cycle genes in HCC cells. We further confirmed that SNORD52 upregulated CDK1 by enhancing the stability of CDK1 proteins and that the function of SNORD52 depends on the presence of CDK1. Conclusion: Overall, the present study indicates that SNORD52 could be a potential biomarker for HCC. Targeting the Upf1/SNORD52/CDK1 pathway might have therapeutic potential for HCC.

show abstract

“…IHC staining was performed as previously described. 51,52 The slides from pretreatment and posttreatment biopsies were de-waxed and rehydrated. The antigens were retrieved, and the slides were permeabilised and blocked before hybridisation with mouse anti-CD4 antibody (Cat# ZM-0418; ZSGB-Bio, Beijing, China), rabbit anti-CD8 antibody (Cat# ZA-0508; ZSGB-Bio), mouse anti-CD68 antibody (Cat# ab201340; Abcam, Cambridge, MA, USA), mouse anti-PD-L1/CD274 antibody (Cat# 66248-1-Ig; ProteinTech, Chicago, IL, USA), rabbit anti-RBPJL antibody (Cat# LS-C162508; LS Bio, Seattle, WA, USA), rabbit anti-IL-16 antibody (Cat# DF6600; Affinity Biosciences, Cincinnati, OH, USA), mouse anti-Ki-67 antibody (Cat# 9449; Cell Signaling Technology, Danvers, MA, USA), rabbit anti-CD4 antibody (Cat# 25229; Cell Signaling Technology) and rabbit anti-CD8 antibody (Cat# 98941; Cell Signaling Technology) at 4°C overnight, followed by incubation with biotinylated goat anti-rabbit/mouse immunoglobulin (GK500705, Dako, Glostrup, Denmark) at 37°C for 30 min.…”

Section: Ihc Stainingmentioning

confidence: 99%

p.P476S mutation of RBPJL inhibits the efficacy of anti‐PD‐1 therapy in oesophageal squamous cell carcinoma by blunting T‐cell responses

et al. 2020

Self Cite

View full text Add to dashboard Cite

Objectives. Anti-PD-1 immune checkpoint blockade represents the onset of a new era in cancer immunotherapy. However, robust predictors are necessary for screening patients with immune checkpoint-responsive oesophageal squamous cell carcinoma (ESCC). Methods. We obtained biopsy samples from an ESCC patient with mixed responses. The expression of CD4, CD8, CD68, PD-L1, RBPJL and IL-16 was analysed by immunohistochemistry, and the correlation with prognostic value was obtained from the GEPIA portal. T-cell functions were examined by flow cytometry, MTS and transwell assays. The secreted cytokines were identified using an Inflammation Array Kit. The concentration of soluble IFNγ was measured by enzyme-linked immunosorbent assay. The clinical benefit of RBPJL was examined in a PBMC xenograft mouse model. Results. The patient had an exceptional clinical response with shrinkage of the primary oesophageal and lung metastatic lesions as well as enlargement of liver metastatic lesions after toripalimab monotherapy. Four liver-specific gene mutations were identified. RBPJL showed better response to toripalimab in the PBMC cell-derived xenograft (CDX) ESCC model. Conditional medium from RBPJL overexpression induced chemotaxis and proliferation of T lymphocytes, as well as Th2/Th1 differentiation through the RBPJL-NF-κB-IL-16 axis in vitro. These functions were all inhibited by the p.P476S mutation of RBPJL (RBPJL (p.P476S)). Conclusions. We report for the first time that RBPJL (p.P476S) promotes tumor growth in ESCC and inhibits the efficacy of anti-PD-1 therapy through blunting T-cell responses. Our findings provide a potential new predictor for evaluating the efficacy of anti-PD-1 therapy in ESCC patients.

show abstract

Long noncoding RNA AGPG regulates PFKFB3-mediated tumor glycolytic reprogramming

Cited by 136 publications

References 59 publications

VDR–SOX2 signaling promotes colorectal cancer stemness and malignancy in an acidic microenvironment

VDR–SOX2 signaling promotes colorectal cancer stemness and malignancy in an acidic microenvironment

The C/D box small nucleolar RNA SNORD52 regulated by Upf1 facilitates Hepatocarcinogenesis by stabilizing CDK1

p.P476S mutation of RBPJL inhibits the efficacy of anti‐PD‐1 therapy in oesophageal squamous cell carcinoma by blunting T‐cell responses

Contact Info

Product

Resources

About