Hypoxia-induced lncRNA RP11-390F4.3 promotes epithelial-mesenchymal transition (EMT) and metastasis through upregulating EMT regulators

Peng, Pei-Hua; Lai, Joseph Chieh-Yu; Hsu, Kai-Wen; Wu, Kou-Juey

doi:10.1016/j.canlet.2020.04.014

Cited by 49 publications

(63 citation statements)

References 30 publications

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“…LncRNA MALAT1 has previously been regarded as a metastasis-promoting factor in various tumors, but it is a metastasis-suppressing factor in breast cancer through binding and inactivating the pro-metastatic transcription factor TEAD ( Kim et al, 2018 ). LncRNA RP11-390F4.3 is induced by hypoxia/HIF-1α to facilitate EMT through modulation of multiple EMT-associated factors, leading to tumor metastasis ( Peng et al, 2020 ). In addition, m6A has been identified as the most common chemical modification manner for various RNAs in eukaryotic cells, and it is involved in the progression of tumor through relative key regulatory factors with m6A modification ( Wang Q. et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Hub Long Noncoding RNAs with m6A Modification for Signatures and Prognostic Values in Kidney Renal Clear Cell Carcinoma

Lin

Wang

et al. 2021

Front. Mol. Biosci.

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Background: N6-methyladenosine (m6A)–modified long noncoding RNAs (m6A-lncRNAs) have been proven to be involving in regulating tumorigenesis, invasion, and metastasis for a variety of tumors. The present study aimed to screen lncRNAs with m6A modification and investigate their biological signatures and prognostic values in kidney renal clear cell carcinoma (KIRC).Materials and Methods: lncRNA-seq, miRNA-seq, and mRNA-seq profiles of KIRC samples and the clinical characteristics of corresponding patients were downloaded from The Cancer Genome Atlas (TCGA). The R package “edgeR” was utilized to perform differentially expressed analysis on these profiles to gain DElncRNAs, DEmiRNAs, and DEmRNAs, respectively. The results of intersection of DElncRNAs and m6A-modified genes were analyzed by the weighted gene co-expression network analysis (WGCNA) to screen hub m6A-lncRNAs. Then, WGCNA was also used to construct an lncRNA-miRNA-mRNA (ceRNA) network. The Cox regression analysis was conducted on hub m6A-lncRNAs to construct the m6A-lncRNAs prognostic index (m6AlRsPI). Receiver operating characteristic (ROC) curve was used to assess the predictive ability of m6AlRsPI. The m6AlRsPI model was tested by internal and external cohorts. The molecular signatures and prognosis for hub m6A-lncRNAs and m6AlRsPI were analyzed. The expression level of hub m6A-lncRNAs in KIRC cell lines were quantified by qRT-PCR.Results: A total of 21 hub m6A-lncRNAs associated with tumor metastasis were identified in the light of WGCNA. The ceRNA network for 21 hub m6A-lncRNAs was developed. The Cox regression analysis was performed on the 21 hub m6A-lncRNAs, screening two m6A-lncRNAs regarded as independent prognostic risk factors. The m6AlRsPI was established based on the two m6A-lncRNAs as follows: (0.0006066 × expression level of LINC01820) + (0.0020769 × expression level of LINC02257). The cutoff of m6AlRsPI was 0.96. KM survival analysis for m6AlRsPI showed that the high m6AlRsPI group could contribute to higher mortality. The area under ROC curve for m6AlRsPI for predicting 3- and 5-year survival was 0.760 and 0.677, respectively, and the m6AlRsPI was also tested. The mutation and epithelial–mesenchymal transition (EMT) analysis for m6AlRsPI showed that the high m6AIRsPI group had more samples with gene mutation and had more likely caused EMT. Finally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed for mRNAs interacted with the two m6A-lncRNAs, showing they were involved in the process of RNA splicing and regulation of the mRNA surveillance pathway. qRT-PCR analysis showed that the two m6A-lncRNAs were upregulated in KIRC.Conclusion: In the present study, hub m6A-lncRNAs were determined associated with metastasis in KIRC, and the ceRNA network demonstrated the potential carcinogenic regulatory pathway. Two m6A-lncRNAs associated with the overall survival were screened and m6AlRsPI was constructed and validated. Finally, the molecular signatures for m6AlRsPI and the two m6A-lncRNAs were analyzed to investigate the potential modulated processes in KIRC.

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Section: Discussionmentioning

confidence: 99%

Hub Long Noncoding RNAs with m6A Modification for Signatures and Prognostic Values in Kidney Renal Clear Cell Carcinoma

Lin

Wang

et al. 2021

Front. Mol. Biosci.

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“…For example, MEG3 suppresses tumor development by modulating EMT and cell adhesion 21 . LncRNA RP11‐390F4.3 upregulates EMT‐associated regulators and promotes metastasis and EMT process 22 . In colon cancer, knockdown of LINC00460 could downregulate ANXA2 and represses EMT process 23 .…”

Section: Discussionmentioning

confidence: 99%

High expression of novel biomarker KRT16P3 promotes the progression of tongue squamous cell carcinoma and predicts poor prognosis

Yang

Wang

et al. 2021

J Oral Pathology Medicine

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Background Overexpression of long non‐coding RNAs (lncRNAs) reveals the abnormal pathological processes in many human cancers. KRT16P3, a novel overexpressed lncRNA in tongue squamous cell carcinoma (TSCC), was identified by previous lncRNA microarrays. However, the role of KRT16P3 in TSCC is not clear. Methods Quantitative real‐time polymerase chain reaction (qRT‐PCR) was used to detect the expression of KRT16P3 in TSCC tissues and cells. Next, the relationships between KRT16P3 and the clinical significance of TSCC patients were analyzed. Additionally, Cell Counting Kit‐8, 5‐Bromo‐2‐deoxyuridine (BrdU) incorporation assay, cell colony formation assay, flow cytometry cell apoptosis analysis, scratch wound healing assay, transwell invasion assay were used to explore the biological function of KRT16P3. Western blot and qRT‐PCR were used to determine the expression of epithelial‐mesenchymal transition (EMT) markers. The pathway changes after KRT16P3 knockdown were detected by Western blot. Results We found KRT16P3 expression is significantly upregulated in TSCC tissues and positively associated with advanced clinicopathological features of TSCC patients, and it may serve as a poor prognostic factor. Functionally, KRT16P3 knockdown inhibits proliferation, migration, invasion and promotes apoptosis of TSCC cells. Furthermore, we also revealed that KRT16P3 knockdown suppresses EMT and JAK2/STAT3 signaling pathway. Conclusion Our results validated that KRT16P3 can modulate the malignant progression, EMT process, and JAK2/STAT3 signaling pathway of TSCC, which might also serve as a novel prognostic biomarker and an attractive target for TSCC patients.

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“…Western blotting analysis of EMT markers was based on a previously published method with slight modifications. 11 CNE1 cells were digested using radioimmunoprecipitation assay cracking liquid (Beyotime Biotechnology, Shanghai, China) and collected proteins were preliminarily separated by sodium dodecyl sulfate–polyacrylamide gel electrophoresis and transferred to a polyvinylidene fluoride membrane. The membrane was washed twice with phosphate-buffered saline (PBS) and incubated in blocking liquid for 2 hours.…”

Section: Methodsmentioning

confidence: 99%

Long non-coding (lnc)RNA profiling and the role of a key regulator lnc-PNRC2-1 in the transforming growth factor-β1-induced epithelial–mesenchymal transition of CNE1 nasopharyngeal carcinoma cells

et al. 2021

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Objectives To identify key long non-coding (lnc)RNAs responsible for the epithelial–mesenchymal transition (EMT) of CNE1 nasopharyngeal carcinoma cells and to investigate possible regulatory mechanisms in EMT. Methods CNE1 cells were divided into transforming growth factor (TGF)-β1-induced EMT and control groups. The mRNA and protein expression of EMT markers was determined by real-time quantitative PCR and western blotting. Differentially expressed genes (DEGs) between the two groups were identified by RNA sequencing analysis, and DEG functions were analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses. EMT marker expression was re-evaluated by western blotting after knockdown of a selected lncRNA. Results TGF-β1-induced EMT was characterized by decreased E-cadherin and increased vimentin, N-cadherin, and Twist expression at both mRNA and protein levels. Sixty lncRNA genes were clustered in a heatmap, and mRNA expression of 14 dysregulated lncRNAs was consistent with RNA sequencing. Knockdown of lnc-PNRC2-1 increased expression of its antisense gene MYOM3 and reduced expression of EMT markers, resembling treatment with the TGF-β1 receptor inhibitor LY2109761. Conclusion Various lncRNAs participated indirectly in the TGF-β1-induced EMT of CNE1 cells. Lnc-PNRC2-1 may be a key regulator of this and is a potential target to alleviate CNE1 cell EMT.

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Hypoxia-induced lncRNA RP11-390F4.3 promotes epithelial-mesenchymal transition (EMT) and metastasis through upregulating EMT regulators

Cited by 49 publications

References 30 publications

Hub Long Noncoding RNAs with m6A Modification for Signatures and Prognostic Values in Kidney Renal Clear Cell Carcinoma

Hub Long Noncoding RNAs with m6A Modification for Signatures and Prognostic Values in Kidney Renal Clear Cell Carcinoma

High expression of novel biomarker KRT16P3 promotes the progression of tongue squamous cell carcinoma and predicts poor prognosis

Long non-coding (lnc)RNA profiling and the role of a key regulator lnc-PNRC2-1 in the transforming growth factor-β1-induced epithelial–mesenchymal transition of CNE1 nasopharyngeal carcinoma cells

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