Abstract
Gastric cancer (GC) is a heterogeneous disease at the molecular and clinical levels. The diffuse subtype is associated with more aggressive behavior and poor prognosis than the intestinal subtype. Epithelial-to-mesenchymal transition (EMT) may be involved in the diffuse mesenchymal phenotype. Long non-coding RNA (lncRNA) deregulation plays a vital role in GC development and progression. Here, we aimed to comprehensively disclose lncRNAs associated with GC diffuse/mesenchymal type. RNA-sequencing expression profiles of patients with stomach adenocarcinoma and the corresponding clinical data were downloaded from The Cancer Genome Atlas database. Differentially expressed lncRNAs related to tumor samples and diffuse subtype were identified. The lncRNA activating regulator of DKK1 (LNCAROD) was experimentally studied. Furthermore, a lncRNA-miRNA-mRNA network was constructed to identify potential biological functions of LNCAROD. LNCAROD expression was detected by reverse transcription-quantitative polymerase chain reaction in GC cell lines. LNCAROD expression was silenced using the small interference RNA strategy. Cell proliferation and migration were evaluated using colony formation assay, scratch wound healing, and Transwell migration assays. LNCAROD was significantly upregulated in some GC cells. The knocking down of LNCAROD significantly reduced cell proliferation and migration. LNCAROD-miR-181-PROX1 axis was introduced as a potential regulatory mechanism by which LNCAROD may exert its functions in cells. Our findings highlight that LNCAROD is involved in cell proliferation and migration in GC and supports its implicit role in regulating EMT. It may serve as a potential diagnostic and therapeutic target in GC. In addition, LNCAROD may function through the possible regulatory axis in GC development.
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Acknowledgements
The authors would like to thank Isfahan University of Medical Sciences and the Iran National Science Foundation (INSF) for funding this work through grant numbers 397114 and 96013247, respectively. The data and results shown here are partly based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga.
Funding
The authors disclosed receipt of the following financial support for the research: This work was supported by the Isfahan University of Medical Sciences (grant number 397114), and the Iran National Science Foundation (INSF) (grant number 96013247).
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All authors participated in the design, interpretation of the studies, analysis of the data, and review of the manuscript; Sara Ansari and Parvaneh Nikpour conceived and designed the research, Sara Ansari collected the data and conducted the experiments, Sara Ansari and Parvaneh Nikpour performed the analysis, and Sara Ansari and Parvaneh Nikpour wrote the manuscript.
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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Isfahan University of Medical Sciences, Isfahan, Iran (Date 02/09/2018. /No: IR.MUI.RESEAECH.REC.1397.116).
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Ansari, S., Nikpour, P. LNCAROD promotes the proliferation and migration of gastric cancer: a bioinformatics analysis and experimental validation. Funct Integr Genomics 23, 34 (2023). https://doi.org/10.1007/s10142-022-00954-5
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DOI: https://doi.org/10.1007/s10142-022-00954-5