Enhanced expression of lncRNA TP73-AS1 predicts unfavorable prognosis for gastric cancer and promotes cell migration and invasion by induction of EMT

Zhang, Wei; Zhai, Yajuan; Wang, Wenbin; Cao, Min; Ma, Chunjie

doi:10.1016/j.gene.2018.08.055

Cited by 31 publications

(13 citation statements)

References 28 publications

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“…Several previous studies have revealed that some of these lncRNAs participate in solid tumor risky progression. For example, high TP73-AS1 expression is associated with poor prognosis, and inhibiting TP73-AS1 expression suppresses EMT in gastric cancer and bladder cancer [37,38]. Overexpressing CRNDE promotes EMT in oral epithelial cell carcinoma and osteosarcoma [39,40].…”

Section: Discussionmentioning

confidence: 99%

Profiling pro-neural to mesenchymal transition identifies a lncRNA signature in glioma

Liang

Guan

et al. 2020

J Transl Med

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Background Molecular classification has laid the framework for exploring glioma biology and treatment strategies. Pro-neural to mesenchymal transition (PMT) of glioma is known to be associated with aggressive phenotypes, unfavorable prognosis, and treatment resistance. Recent studies have highlighted that long non-coding RNAs (lncRNAs) are key mediators in cancer mesenchymal transition. However, the relationship between lncRNAs and PMT in glioma has not been systematically investigated. Methods Gene expression profiles from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), GSE16011, and Rembrandt with available clinical and genomic information were used for analyses. Bioinformatics methods such as weighted gene co-expression network analysis (WGCNA), gene set enrichment analysis (GSEA), Cox analysis, and least absolute shrinkage and selection operator (LASSO) analysis were performed. Results According to PMT scores, we confirmed that PMT status was positively associated with risky behaviors and poor prognosis in glioma. The 149 PMT-related lncRNAs were identified by WGCNA analysis, among which 10 (LINC01057, TP73-AS1, AP000695.4, LINC01503, CRNDE, OSMR-AS1, SNHG18, AC145343.2, RP11-25K21.6, RP11-38L15.2) with significant prognostic value were further screened to construct a PMT-related lncRNA risk signature, which could divide cases into two groups with distinct prognoses. Multivariate Cox regression analyses indicated that the signature was an independent prognostic factor for high-grade glioma. High-risk cases were more likely to be classified as the mesenchymal subtype, which confers enhanced immunosuppressive status by recruiting macrophages, neutrophils, and regulatory T cells. Moreover, six lncRNAs of the signature could act as competing endogenous RNAs to promote PMT in glioblastoma. Conclusions We profiled PMT status in glioma and established a PMT-related 10-lncRNA signature for glioma that could independently predict glioma survival and trigger PMT, which enhanced immunosuppression.

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Section: Discussionmentioning

confidence: 99%

Profiling pro-neural to mesenchymal transition identifies a lncRNA signature in glioma

Liang

Guan

et al. 2020

J Transl Med

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“…LncRNA P73 antisense RNA 1T (TP73-AS1) is located on chromosome 1p36.32 of the human genome. It has been reported that lncRNA TP73-AS1 is overexpressed in non-small lung cancer [7], esophageal squamous cell carcinoma [8], gastric cancer [9–11], glioblastoma [12,13], glioma tissue [14], hepatocellular carcinoma [15], breast cancer [16,17], colorectal cancer [18], and ovarian cancer [19], but is down-regulated in bladder cancer tissue [20]. It has also been found that the knockdown of lncRNA TP73-AS1 attenuates the proliferation of esophageal cancer cells and enhances their chemosensitivity by inhibiting the expression of 3-hydroxybutyrate dehydrogenase type 2 (BDH2) [8].…”

Section: Introductionmentioning

confidence: 99%

LncRNA TP73-AS1 sponges miR-141-3p to promote the migration and invasion of pancreatic cancer cells through the up-regulation of BDH2

Cui

Wang

et al. 2019

Bioscience Reports

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LncRNA TP73 antisense RNA 1T (TP73-AS1) plays an important role in human malignancies. However, the levels of TP73-AS1 and its functional mechanisms in pancreatic cancer metastasis remain unknown, and the clinical significance of TP73-AS1 in human pancreatic cancer is also unclear. In the present study, the levels of TP73-AS1 and its candidate target miR-141 in pancreatic cancer and adjacent normal tissue were detected using qRT-PCR. The association between TP73-AS1 levels and the clinicopathologic characteristics of pancreatic cancer patients were analyzed. The relationship between TP73-AS1 and miR-141, and miR-141 and its candidate target 3-hydroxybutyrate dehydrogenase type 2 (BDH2) was confirmed using dual-luciferase reporter assays. TP73-AS1 and/or miR-141 were knocked down using siRNA or an inhibitor in pancreatic cancer cells and cell migration and invasion then examined. The results showed that TP73-AS1 was up-regulated in pancreatic cancer tissue and cell lines. High levels of TP73-AS1 were correlated with poor clinicopathological characteristics and shorter overall survival. MiR-141 was a direct target for TP73-AS1, while BDH2 was a direct target for miR-141. The knockdown of TP73-AS1 significantly inhibited the migration and invasion of pancreatic cancer cells, while the miR-141 inhibitor significantly restored the migration and invasion. Therefore, TP73-AS1 positively regulated BDH2 expression by sponging miR-141. These findings suggest that TP73-AS1 serves as an oncogene and promotes the metastasis of pancreatic cancer. Moreover, TP73-AS1 could serve as a predictor and a potential drug biotarget for pancreatic cancer.

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“…lncRNAs have also been reported to serve as markers of tumor development, progression and prognosis in numerous types of cancer. For instance, lncRNA TP73-AS1 was reported to be upregulated in tumor tissue and to be associated with larger tumor size, TNM stage and shorter OS in gastric cancer patients (31). lncRNA serine peptidase inhibitor, Kunitz type 1-AS1 was determined to be overexpressed in cancer tissue and to be associated with a higher risk of regional lymph node metastasis and distant metastasis, and it is also an independent predictor of shorter relapse-free survival in colorectal cancer patients (32).…”

Section: Discussionmentioning

confidence: 99%

lnc-PKD2-2-3, identified by long non-coding RNA expression profiling, is associated with pejorative tumor features and poor prognosis, enhances cancer stemness and may serve as cancer stem-cell marker in cholangiocarcinoma

Qiu

et al. 2019

Int J Oncol

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The present study aimed to explore the long non-coding RNA (lncRNA) expression profiles and correlation of lnc-PKD2-2-3 with tumor features and prognosis, and to investigate its effect on regulating cancer-cell stemness and its potential as a cancer stem cell (CSC) marker in cholangiocarcinoma (CCA). lncRNA expression profiles were determined in 3 pairs of CCA tumors and adjacent tissues by microarray analysis, and lnc-PKD2-2-3 expression was then validated in 60 paired samples by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Expression of common CSC markers [(CD44, CD133 and octamer-binding transcription factor 4 (OCT4)], CD44 + CD133 + cell proportions, sphere formation efficiency and drug resistance to 5-fluorouracil (5-FU) were measured following ectopic overexpression of lnc-PKD2-2-3 or silencing via small hairpin RNA lentivirus transfection into the TFK-1 and Huh-28 CCA cell lines. Finally, lnc-PKD2-2-3 expression was measured in CCA stem-like cells and normal CCA cells. The results from the microarray analysis identified a total of 4,223 upregulated and 4,596 downregulated lncRNAs between CCA tumor tissue and paired adjacent tissue, which were enriched in regulating cancer-associated pathways. RT-qPCR validation revealed that lnc-PKD2-2-3 was upregulated in CCA and associated with a higher Eastern Cooperative Oncology Group performance score, poor differentiation, advanced TNM stage, increased carcinoembryonic antigen and poor overall survival in CCA patients. In vitro , lnc-PKD2-2-3 increased CD44, CD133 and OCT4 expression as well as the CD44 + CD133 + cell proportion, raised the sphere formation efficiency and enhanced drug resistance to 5-FU in TFK-1 and Huh-28 cells. In addition, lnc-PKD2-2-3 was positively correlated with CSC markers in CCA tumor tissues and was markedly upregulated in CCA stem-like cells compared with that in normal CCA cells. In conclusion, lnc-PKD2-2-3, selected by lncRNA expression profiling, was associated with pejorative tumor features and poor prognosis, enhanced cancer stemness and may serve as a CSC marker in CCA.

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Enhanced expression of lncRNA TP73-AS1 predicts unfavorable prognosis for gastric cancer and promotes cell migration and invasion by induction of EMT

Cited by 31 publications

References 28 publications

Profiling pro-neural to mesenchymal transition identifies a lncRNA signature in glioma

Profiling pro-neural to mesenchymal transition identifies a lncRNA signature in glioma

LncRNA TP73-AS1 sponges miR-141-3p to promote the migration and invasion of pancreatic cancer cells through the up-regulation of BDH2

lnc-PKD2-2-3, identified by long non-coding RNA expression profiling, is associated with pejorative tumor features and poor prognosis, enhances cancer stemness and may serve as cancer stem-cell marker in cholangiocarcinoma

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