NR2F1-AS1 Promotes Pancreatic Ductal Adenocarcinoma Progression Through Competing Endogenous RNA Regulatory Network Constructed by Sponging miRNA-146a-5p/miRNA-877-5p

Luo, Dong; Liu, Yunfei; Li, Zhiqiang; Zhu, Hongwei; Yu, Xiao

doi:10.3389/fcell.2021.736980

Cited by 10 publications

(15 citation statements)

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“…BARX1 was hypermethylated in some patients with CRC ( 33 ), and its expression was a predictor of relapse-free survival for gastrointestinal stromal tumors ( 34 ). ZNF532 has been linked to the prognosis of pancreatic ductal adenocarcinoma ( 35 ). HEYL modulates the metastasis forming capacity of CRC ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

A Transcription Factor Signature Can Identify the CMS4 Subtype and Stratify the Prognostic Risk of Colorectal Cancer

et al. 2022

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BackgroundColorectal cancer (CRC) is a heterogeneous disease, and current classification systems are insufficient for stratifying patients with different risks. This study aims to develop a generalized, individualized prognostic consensus molecular subtype (CMS)-transcription factors (TFs)-based signature that can predict the prognosis of CRC.MethodsWe obtained differentially expressed TF signature and target genes between the CMS4 and other CMS subtypes of CRC from The Cancer Genome Atlas (TCGA) database. A multi-dimensional network inference integrative analysis was conducted to identify the master genes and establish a CMS4-TFs-based signature. For validation, an in-house clinical cohort (n = 351) and another independent public CRC cohort (n = 565) were applied. Gene set enrichment analysis (GSEA) and prediction of immune cell infiltration were performed to interpret the biological significance of the model.ResultsA CMS4-TFs-based signature termed TF-9 that includes nine TF master genes was developed. Patients in the TF-9 high-risk group have significantly worse survival, regardless of clinical characteristics. The TF-9 achieved the highest mean C-index (0.65) compared to all other signatures reported (0.51 to 0.57). Immune infiltration revealed that the microenvironment in the high-risk group was highly immune suppressed, as evidenced by the overexpression of TIM3, CD39, and CD40, suggesting that high-risk patients may not directly benefit from the immune checkpoint inhibitors.ConclusionsThe TF-9 signature allows a more precise categorization of patients with relevant clinical and biological implications, which may be a valuable tool for improving the tailoring of therapeutic interventions in CRC patients.

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Section: Discussionmentioning

confidence: 99%

A Transcription Factor Signature Can Identify the CMS4 Subtype and Stratify the Prognostic Risk of Colorectal Cancer

et al. 2022

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“…Yu et al discovered that circ_0061395 promoted HCC advancement by sponging miR-877-5p and increasing PIK3R3 expression [ 44 ]. Luo et al uncovered that miR-877-5p restrains PDAC progression via negatively regulating lncRNA NR2F1-AS1 [ 45 ]. Additionally, researchers have confirmed miR-877-5p as a positive element in other malignancies [ 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

circCRKL, a circRNA derived from CRKL, regulates BCR-ABL via sponging miR-877-5p to promote chronic myeloid leukemia cell proliferation

et al. 2022

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Background The BCR-ABL fusion protein is the key factor that results in the occurrence of chronic myeloid leukemia (CML). Imatinib (IM) is a targeted inhibitor of BCR-ABL to achieve complete remission. However, remission failure occurs due to acquired resistance caused by secondary BCR-ABL mutations, underlining the need for novel BCR-ABL-targeting strategies. Circular RNAs (circRNAs) derived from tumor-related genes have been revealed as possible therapeutic targets for relevant cancers in recent investigations. In CML, the roles of this kind of circRNA are yet obscure. Methods Firstly, RT-qPCR was used for determining circCRKL expression level in cell lines and clinical samples, RNase R and Actinomycin D were employed to verify the stability of circCRKL. Then shRNAs were designed to specifically knockdown circCRKL. The function of circCRKL in vitro was investigated using CCK-8, colony formation assay, and flow cytometry, while a CML mouse model was constructed to explore the function in vivo. Finally, a dual-luciferase reporter assay, RNA pull-down, RNA immunoprecipitation, and rescue experiments were conducted to investigate the mechanism of circCRKL functioning. Results Here, we determined circCRKL, which derives from CML-relevant gene CRKL, is over-expressed in BCR-ABL+ cells. Then we noticed knocking down circCRKL using shRNA lentivirus dampens the proliferation of BCR-ABL+ cells both in vitro and in vivo, and augments susceptibility of resistant cells to IM. Intriguingly, we observed that circCRKL has a considerable impact on the expression level of BCR-ABL. Mechanistically, circCRKL could behave like a decoy for miR-877-5p to enhance the BCR-ABL level, allowing BCR-ABL+ cells to maintain viability. Conclusions Overall, the current study uncovers that circCRKL is specifically expressed and regulates BCR-ABL expression level via decoying miR-877-5p in BCR-ABL+ cells, highlighting that targeting circCRKL along with imatinib treatment could be utilized as a potential therapeutic strategy for CML patients.

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“…to regulate the expression of nine target genes including NRP2 gene and participate in the regulation of PDAC development (Luo et al 2021). At present, there is no study on miR-146a-5p in OCSCs, but the miR-146a-5p derived from mesenchymal stem cells exosome has been reported to be able to enhance the sensitivity of ovarian cancer cells to docetaxel and taxane (Qiu et al 2020).…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of ovarian cancer stem cells-associated lncRNA-miRNA-mRNA network via microarray and Gene Expression Omnibus database

Liu

Bai

et al. 2022

Preprint

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Background Competing endogenous RNAs (CeRNAs) play an important role in maintenance of ovarian cancer stem cells (OCSCs) characteristics. Objective To isolate a new OCSC line and construct a ceRNA network for maintenance of OCSCs characteristics by the cell line and GEO Database. Methods We isolated OCSCs from ovarian cancer cell line COC1 by chemotherapy drugs and growth factors. We identified the DEMs, DELs and DEGs between OCSCs and COC1 by microarray and combined them with representative microarray profiles in GEO Database. The ceRNA network was constructed by STRING and Cytoscape. QPCR and western blot were used to verify the expression of several genes that contained in the predicted network. Results According to the combination, 28 DEMs were identified at first, and 452 DEGs were obtained combining with the predicted targets of these miRNAs and our mRNA microarray results. Up-regulated DEGs of them were significantly enriched in ‘p53 signaling pathway’, ‘FoxO signaling pathway’, et al, whereas down-regulated DEGs were significantly enriched in ‘Adherens junction’ and ‘Hepatitis C’ pathway. Finally, we obtained OCSCs characteristics related ceRNA network with 10 DEMs, 21 DEGs, and 25 transcripts of 13 DELs. We verified that LINC00665-miR-146a-5p-NRP2 should be one of the pathways of the constructed ceRNA network. Conclusion The ceRNA network we constructed may be involved in the stem cell characteristics maintenance of OCSCs and provide directions for further OCSCs research in the future.

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NR2F1-AS1 Promotes Pancreatic Ductal Adenocarcinoma Progression Through Competing Endogenous RNA Regulatory Network Constructed by Sponging miRNA-146a-5p/miRNA-877-5p

Cited by 10 publications

References 83 publications

A Transcription Factor Signature Can Identify the CMS4 Subtype and Stratify the Prognostic Risk of Colorectal Cancer

A Transcription Factor Signature Can Identify the CMS4 Subtype and Stratify the Prognostic Risk of Colorectal Cancer

circCRKL, a circRNA derived from CRKL, regulates BCR-ABL via sponging miR-877-5p to promote chronic myeloid leukemia cell proliferation

Integrated analysis of ovarian cancer stem cells-associated lncRNA-miRNA-mRNA network via microarray and Gene Expression Omnibus database

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