HOTTIP functions as an independent biomarker in multiple cancers. However, the role of HOTTIP in hepatocellular carcinoma (HCC) remains unclear. In this study, we sought to investigate the HOTTIP expression in HCC and normal liver. We combined quantitative reverse transcription-polymerase chain reactions (qRT-PCR), Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), Multi Experiment Matrix (MEM) and Oncomine database to assess the clinical role and the potential molecular mechanism of HOTTIP in HCC. Furthermore, a meta-analysis was performed to evaluate the relationship between HOTTIP and HCC tumorigenesis and development. Additionally, bioinformatics analysis, which contained Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and network analysis, were applied to investigate the underlying functions, pathways and networks of the potential genes. HOTTIP was obviously upregulated in HCC. A statistically significant higher expression of HOTTIP was found in TNM (III +IV), age (≥60), sex (male), race (white) and cirrhosis (no) compared to the control groups (P<0.05). Furthermore, the meta-analysis of 393 cases from multiple centers indicated that HOTTIP had high diagnostic value in HCC. Additionally, according to GO and KEGG analyses, we found that the most strongly enriched functional terms were gland development, transcription factor activity and extrinsic to membrane. Also, the HOTTIP co-expressed genes were significantly related to PPAR signaling pathway. We speculate that HOTTIP might play a vital part in HCC via regulating various pathways, especially PPAR signaling pathway. However, the detailed mechanism should be confirmed by functional experiments.
Hypertrophic scaring (HS) is a dermal fibroproliferative disorder characterized by excessive deposition of collagen and other extracellular matrix (ECM) components. The aim of this study is to explore crucial lncRNAs and circRNAs associated with HS and provide a better understanding of the molecular mechanism of HS. To investigate the lncRNA, circRNA and mRNA expression profiles we performed RNA-sequencing of human HS and normal skin tissues. Following the identification of differentially expressed mRNAs (DEmRNAs), lncRNAs (DElncRNAs) and circRNAs (DEcircRNAs), we performed functional enrichment of DEmRNAs. Further on, we constructed DElncRNA/DEcircRNA-DEmRNA co-expression networks and ceRNA regulatory networks and performed functional analyses of the DEmRNAs in the constructed networks. In total, 487 DEmRNAs, 92 DElncRNAs and 17 DEcircRNAs were identified. DEmRNAs were significantly enriched in processes like collagen fibril organization, ECM-receptor interaction and PI3K-Akt signaling pathway. Additionally, we detected 580 DElncRNA-DEmRNA and 505 DEcircRNA-DEmRNA co-expression pairs The ceRNA network contained 18 circRNA-miRNA pairs, 18 lncRNA-miRNA pairs and 409 miRNA-mRNA pairs, including 10 circRNAs, 5 lncRNAs, 15 miRNAs, and 160 mRNAs. We concluded that MIR503HG/hsa-miR-204-3p/ACAN, MIR503HG/hsa-miR-431-5p/TNFRSF9, MEG3/hsa-miR-6884-5p/ADAMTS14, AC000035.1-ADAMTS14 and hsa_circ_0069865-COMP/ADAM12 interaction pairs may play a central role in HS.
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