Long non-coding RNA ZFAS1 is a major regulator of epithelial-mesenchymal transition through miR-200/ZEB1/E-cadherin, vimentin signaling in colon adenocarcinoma

O’Brien, Stephen J.; Fiechter, Casey; Burton, James F.; Hallion, Jacob; Paas, Mason; Patel, Ankur; Patel, Anand; Rochet, Andre; Scheurlen, Katharina M.; Gardner, Sarah; Eichenberger, M. Robert; Sarojini, Harshini; Srivastava, Sudhir; Rai, Shesh; Kalbfleisch, Theodore S.; Polk, Hiram C.; Galandiuk, Susan

doi:10.1038/s41420-021-00427-x

Cited by 27 publications

(30 citation statements)

References 37 publications

(33 reference statements)

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“…ZFAS1 is a major regulator of the epithelial–mesenchymal transition (EMT) through miR-200/ZEB1/E-cadherin and vimentin signaling in colon adenocarcinoma. 28 The expression level of AL031710.1 decreases with the increase in tumor stage of papillary renal cell carcinoma. 29 AL355102.4 is downregulated in clear cell renal cell carcinoma samples and indicates good prognosis when lowly expressed, which reveals that AL355102.4 is a risk factor with high gene expression.…”

Section: Discussionmentioning

confidence: 96%

A Novel Ferroptosis-Related lncRNA Signature for Prognosis Prediction in Patients with Papillary Renal Cell Carcinoma

Dang

Jin

Nan

et al. 2022

IJGM

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Papillary renal cell carcinoma (PRCC) is a common renal cell carcinoma. Recent studies have reported that ferroptosis is involved in the occurrence and development of tumors. Long non-coding RNAs can be used as independent biomarkers for the diagnosis and prognosis of a variety of tumors. Methods: Gene expression profile and clinical information of patients with PRCC were obtained from The Cancer Genome Atlas (TCGA) database. Lasso penalized Cox regression and univariate Cox regression analysis were utilized for model construction. The Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curves were plotted to validate the predictive effect of the prognostic signature. Immune cell infiltration and immune function were compared between the high-risk and low-risk groups. Chemotherapy sensitivity analysis was also performed. Results: We constructed a prognostic signature consisting of 15 ferroptosis-related lncRNAs. The K-M curves validated the fine predictive accuracy of the prognostic signature (p < 0.001). The area under the curve (AUC) of the lncRNA signature was 0.930, exhibiting robust prognostic capacity. The high-risk group had a greater degree of immune cell infiltration than the low-risk group. Significant differences in inflammation promotion, parainflammation, and type I IFN response were noted between the low-risk and high-risk groups (p < 0.01). The expression levels of immune checkpoints including CD80, IDO1, and LAG3 were significantly higher in the high-risk group than in the low-risk group (p < 0.05). Chemotherapy sensitivity analysis showed that MNX1-AS1, ZFAS1, MIR4435-2HG, and ADAMTS9-AS1 were significantly correlated with the sensitivity of some chemotherapy drugs (p < 0.05). Conclusion:We demonstrated that a ferroptosis-related lncRNA prognostic signature could be a novel biomarker for PRCC.

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Section: Discussionmentioning

confidence: 96%

A Novel Ferroptosis-Related lncRNA Signature for Prognosis Prediction in Patients with Papillary Renal Cell Carcinoma

Dang

Jin

Nan

et al. 2022

IJGM

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“…After searching through the publication, we have identified 9 lncRNAs that were suggested to sponge miR-200c in different types of cancer or in other diseases [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 30 ]. Among the identified lncRNAs, we have chosen those that could successfully detect specific products of less than 100 bp using TaqMan probe.…”

Section: Methodsmentioning

confidence: 99%

“…Among the identified lncRNAs, we have chosen those that could successfully detect specific products of less than 100 bp using TaqMan probe. For the purpose of expression analysis, we, therefore, selected the following lncRNAs: LUCAT1 , MALAT1 , lncTCF7 , XIST and ZFAS1 [ 20 , 21 , 22 , 27 , 28 ]. The other four lncRNAs, namely ATB , LINC02582 , N-BLR and ZEB1-AS1 [ 23 , 24 , 25 , 26 ], were excluded from further analysis due to the longer amplification product of pre-designed TaqMan probes.…”

Section: Methodsmentioning

confidence: 99%

“…None of the lncRNAs have yet been proven to directly regulate DCN . In contrast, there are numerous proven lncRNAs that are validated to sponge miR-200c in different cancers, the predicted regulatory miRNA of DCN [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. However, their exact role in regulating miR-200c in CRC has yet to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Differential Expression of Decorin in Metastasising Colorectal Carcinoma Is Regulated by miR-200c and Long Non-Coding RNAs

et al. 2022

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Decorin (DCN) is one of the matricellular proteins that participate in normal cells’ function as well as in cancerogenesis. While its expression in primary tumours is well known, there is limited data about its expression in metastases. Furthermore, the post-transcriptional regulation of DCN is still questionable, although it is well accepted that it is an important mechanism of developing metastatic cancer. The aim of our study was to analyse the expression of DCN and its potential regulatory ncRNAs in metastatic colorectal carcinoma (CRC). Nineteen patients with metastatic CRC were included. Using qPCR, we analysed the expression of DCN, miR-200c and five lncRNAs (LUCAT1, MALAT1, lncTCF7, XIST, and ZFAS1) in lymph node and liver metastases in comparison to the invasive front and central part of a primary tumour. Our results showed insignificant upregulation of DCN and significant upregulation for miR-200c, MALAT1, lncTCF7 and ZFAS1 in metastases compared to the primary tumour. miR-200c showed a positive correlation with DCN, and the aforementioned lncRNAs exhibited a significant positive correlation with miR-200c expression in metastatic CRC. Our results suggest that DCN as well as miR-200c, MALAT1, lncTCF7 and ZFAS1 contribute to the development of metastases in CRC and that regulation of DCN expression in CRC by ncRNAs is accomplished in an indirect manner.

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“…Some lncRNAs are localized in the cytoplasm; they not only interfere with the post-translational modification of proteins and cause abnormal signal transduction but also affect the post-transcriptional expression of mRNAs in the cytoplasm through various mechanisms (e.g., by acting as ceRNAs) ( Chen, 2016 ). Imbalanced expression of some lncRNAs is frequently involved in the progression of numerous malignancies ( O’Brien et al, 2021 ; Wang Y. et al, 2021 ; Zhang et al, 2021 ). Recent studies have reported that lncRNAs are directly or indirectly involved in tumor immune regulation through a variety of mechanisms.…”

Section: Introductionmentioning

confidence: 99%

A Potential Immune-Related Long Non-coding RNA Prognostic Signature for Ovarian Cancer

Pan

2021

Front. Genet.

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Ovarian cancer (OC), the most lethal gynecologic malignancy, ranks fifth in cancer deaths among women, largely because of late diagnosis. Recent studies suggest that the expression levels of immune-related long non-coding RNAs (lncRNAs) play a significant role in the prognosis of OC; however, the potential of immune-related lncRNAs as prognostic factors in OC remains unexplored. In this study, we aimed to identify a potential immune-related lncRNA prognostic signature for OC patients. We used RNA sequencing and clinical data from The Cancer Genome Atlas and the Gene Expression Omnibus database to identify immune-related lncRNAs that could serve as useful biomarkers for OC diagnosis and prognosis. Univariate Cox regression analysis was used to identify the immune-related lncRNAs with prognostic value. Functional annotation of the data was performed through the GenCLiP310 website. Seven differentially expressed lncRNAs (AC007406.4, AC008750.1, AL022341.2, AL133351.1, FAM74A7, LINC02229, and HOXB-AS2) were found to be independent prognostic factors for OC patients. The Kaplan-Meier curve indicated that patients in the high-risk group had a poorer survival outcome than those in the low-risk group. The receiver operating characteristic curve revealed that the predictive potential of the immune-related lncRNA signature for OC was robust. The prognostic signature of the seven lncRNAs was successfully validated in the GSE9891, GSE26193 datasets and our clinical specimens. Multivariate analyses suggested that the signature of the seven lncRNAs was an independent prognostic factor for OC patients. Finally, we constructed a nomogram model and a competing endogenous RNA network related to the lncRNA prognostic signature. In conclusion, our study reveals novel immune-related lncRNAs that may serve as independent prognostic factors in OC.

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Long non-coding RNA ZFAS1 is a major regulator of epithelial-mesenchymal transition through miR-200/ZEB1/E-cadherin, vimentin signaling in colon adenocarcinoma

Cited by 27 publications

References 37 publications

A Novel Ferroptosis-Related lncRNA Signature for Prognosis Prediction in Patients with Papillary Renal Cell Carcinoma

A Novel Ferroptosis-Related lncRNA Signature for Prognosis Prediction in Patients with Papillary Renal Cell Carcinoma

Differential Expression of Decorin in Metastasising Colorectal Carcinoma Is Regulated by miR-200c and Long Non-Coding RNAs

A Potential Immune-Related Long Non-coding RNA Prognostic Signature for Ovarian Cancer

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