c-Myc-activated intronic miR-210 and lncRNA MIR210HG synergistically promote the metastasis of gastric cancer

Li, Zhiyong; Xie, Ying; Deng, Mingxia; Zhu, Leqing; Wu, Xiaobin; Li, Guangqiang; Shi, Nan-Xi; Wen, Chuangyu; Huang, Weicai; Duan, Yuanyuan; Yin, Zhinan; Lin, Xuejia

doi:10.1016/j.canlet.2021.11.006

Cited by 27 publications

(9 citation statements)

References 37 publications

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“…Thus, the development of PTBP1 inhibitors has a potential synergistic effect on reducing tumour resistance to targeted drugs, yet these studies represent another major gap in the field of gastric cancer, and our study attempts to break through the limitations of PTBP1 in the therapeutic field of gastric cancer. Although no PTBP1 inhibitors suitable for gastric cancer treatment were identified, our findings demonstrate that PTBP1 exerts antitumor effects can be mediated through downstream c-Myc, which is one of the key targets for gastric cancer treatment, not only promoting gastric cancer progression and lung metastasis [53], but also involved in the induction of PD-L1 expression [54]. Therefore, the use of c-Myc inhibitors provides ideas for the treatment of gastric cancer and reduction of drug resistance until inhibitors of PTBP1 for gastric cancer are available.…”

Section: Discussionmentioning

confidence: 82%

PTBP1 drives c-Myc-dependent gastric cancer progression and stemness

Chu

et al. 2023

Br J Cancer

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Background Gastric cancer (GC) tumorigenesis and treatment failure are caused by cancer stem cells. Polypyrimidine tract binding protein 1 (PTBP1) was shown to be involved in the development of embryonic stem cells and is now being considered as a therapeutic target for tumour progression and stem-cell characteristics. Methods PTBP1 expression in GC samples was detected using tissue microarrays. Proliferation, colony formation, spheroid formation and stem-cell analysis were used to examine PTBP1’s role in tumorigenesis and stem-cell maintenance. In AGS and HGC-27 cells with or without PTBP1 deficiency, ubiquitin-related protein expression and co-precipitation assays were performed. Results We identified that PTBP1 was aberrantly highly expressed and represented a novel prognostic factor in GC patients. PTBP1 maintained the tumorigenic activity and stem-cell characteristics of GC in vitro and in vivo. PTBP1 directly interacts with c-Myc and stabilises its protein levels by preventing its proteasomal degradation. This is mediated by upregulating the ubiquitin-specific proteases USP28 and limiting FBW7-mediated ubiquitination of c-Myc. Moreover, the depletion of PTBP1-caused tumour regression was significantly compromised by exogenous c-Myc expression. Conclusions By preserving the stability of c-Myc through the ubiquitin–proteasome pathway, the oncogene PTBP1 supports stem-cell-like phenotypes of GC and is involved in GC progression.

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Section: Discussionmentioning

confidence: 82%

PTBP1 drives c-Myc-dependent gastric cancer progression and stemness

Chu

et al. 2023

Br J Cancer

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“…In general, as ceRNAs, the functions of lncRNAs depend on the miRNA target ( 41 - 43 ). Using an online database, GATAD2A was predicted a potential target of miR-3180, which was confirmed by a luciferase reporter assay.…”

Section: Discussionmentioning

confidence: 99%

lncKRT16P6 promotes tongue squamous cell carcinoma progression by sponging miR‑3180 and regulating GATAD2A expression

Zhang

Wang

et al. 2022

Int J Oncol

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Tongue squamous cell carcinoma (TSCC) is characterized by a poor prognosis and its 5-year overall survival rate has not improved significantly. However, the precise molecular mechanisms underlying TSCC remain largely unknown. Through RNA screening, the present study identified a novel long noncoding RNA (lncRNA), keratin 16 pseudogene 6 (lncKRT16P6), which was upregulated in TSCC tissues and cell lines and associated with TSCC tumor stage and differentiation grade. Inhibition of lncKRT16P6 expression reduced TSCC cell migration, invasion and proliferation. lncKRT16P6 sponged microRNA (miR)-3180 and upregulated GATA zinc finger domain containing 2A (GATAD2A) expression. miR-3180 inhibition reversed the lncKRT16P6 depletion-induced attenuation of TSCC malignancy and GATAD2A depletion reversed the miR-3180 silencing-induced enhancement of TSCC malignancy. In summary, the present study revealed a potential competitive endogenous RNA (ceRNA) regulatory pathway in which lncKRT16P6 modulates GATAD2A expression by binding miR-3180, ultimately promoting tumorigenesis and metastasis in TSCC. Therefore, lncKRT16P6 may be used as a prognostic biomarker and therapeutic target for clinical intervention in TSCC.

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“…In addition to pancreatic cancer, MIR210HG can also promote various cancer types, such as breast cancer, gastric cancer, and ovarian cancer (53)(54)(55). Additionally, previous studies have identified seven GT-related lncRNAs as prognostic factors in colon cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Glycosyltransferase-related long non-coding RNA signature predicts the prognosis of colon adenocarcinoma

Zhang

et al. 2022

Front. Oncol.

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PurposeColon adenocarcinoma (COAD) is the most common type of colorectal cancer (CRC) and is associated with poor prognosis. Emerging evidence has demonstrated that glycosylation by long noncoding RNAs (lncRNAs) was associated with COAD progression. To date, however, the prognostic values of glycosyltransferase (GT)-related lncRNAs in COAD are still largely unknown.MethodsWe obtained the expression matrix of mRNAs and lncRNAs in COAD from The Cancer Genome Atlas (TCGA) database. Then, the univariate Cox regression analysis was conducted to identify 33 prognostic GT-related lncRNAs. Subsequently, LASSO and multivariate Cox regression analysis were performed, and 7 of 33 GT-related lncRNAs were selected to conduct a risk model. Gene set enrichment analysis (GSEA) was used to analyze gene signaling pathway enrichment of the risk model. ImmuCellAI, an online tool for estimating the abundance of immune cells, and correlation analysis were used to explore the tumor-infiltrating immune cells in COAD. Finally, the expression levels of seven lncRNAs were detected in colorectal cancer cell lines by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).ResultsA total of 1,140 GT-related lncRNAs were identified, and 7 COAD-specific GT-related lncRNAs (LINC02381, MIR210HG, AC009237.14, AC105219.1, ZEB1-AS1, AC002310.1, and AC020558.2) were selected to conduct a risk model. Patients were divided into high- and low-risk groups based on the median of risk score. The prognosis of the high-risk group was worse than that of the low-risk group, indicating the good reliability and specificity of our risk model. Additionally, a nomogram based on the risk score and clinical traits was built to help clinical decisions. GSEA showed that the risk model was significantly enriched in metabolism-related pathways. Immune infiltration analysis revealed that five types of immune cells were significantly different between groups, and two types of immune cells were negatively correlated with the risk score. Besides, we found that the expression levels of these seven lncRNAs in tumor cells were significantly higher than those in normal cells, which verified the feasibility of the risk model.ConclusionThe efficient risk model based on seven GT-related lncRNAs has prognostic potential for COAD, which may be novel biomarkers and therapeutic targets for COAD patients.

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c-Myc-activated intronic miR-210 and lncRNA MIR210HG synergistically promote the metastasis of gastric cancer

Cited by 27 publications

References 37 publications

PTBP1 drives c-Myc-dependent gastric cancer progression and stemness

PTBP1 drives c-Myc-dependent gastric cancer progression and stemness

lncKRT16P6 promotes tongue squamous cell carcinoma progression by sponging miR‑3180 and regulating GATAD2A expression

Glycosyltransferase-related long non-coding RNA signature predicts the prognosis of colon adenocarcinoma

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