Long non-coding RNA HOTTIP promotes hepatocellular carcinoma tumorigenesis and development: A comprehensive investigation based on bioinformatics, qRT-PCR and meta-analysis of 393 cases

Abstract

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.

<p>MIR22HG As A Tumor Suppressive lncRNA In HCC: A Comprehensive Analysis Integrating RT-qPCR, mRNA-Seq, And Microarrays</p>

“…The process of qRT-PCR has been described in detail in previous studies. [17][18][19] GAPDH served as the reference gene for MIR22HG. Information about the primers for MIR22HG and GAPDH is listed in Table 1.…”

“…Information about the primers for MIR22HG and GAPDH is listed in Table 1. 18,19 MIR22HG expression was calculated by the formula:…”

Analysis of Transcription Factor-Related Regulatory Networks Based on Bioinformatics Analysis and Validation in Hepatocellular Carcinoma

“…Over the last decades, bioinformatics and microarray technology have been widely used to screen the molecular mechanisms of HCC, which provide powerful research support for the diagnosis and treatment of HCC [ 4 – 6 ]. By bioinformatics analysis and microarray technology, functions of some differentially expressed genes (DEGs) in HCC have been explored, which paved the way for exploring complicated process in the occurrence and development of HCC [ 5 , 7 – 9 ]. As an important part of participating in life activities, transcription factors (TFs) have been reported to play an important role in the development of HCC by numerous studies [ 10 , 11 ].…”

Identification of Potential Prognostic Long Non-Coding RNA Biomarkers for Predicting Survival in Patients with Hepatocellular Carcinoma

“…KEGG enrichment analysis revealed a significant enrichment in the PPAR signaling pathway. Zhang et al reported that the lncRNA HOTTIP is upregulated and has a high diagnostic value in HCC, and the genes coexpressed with HOTTIP are related to the PPAR signaling pathway [61]. In a genome-wide Cellular Physiology and Biochemistry Cellular Physiology and Biochemistry analysis of intrahepatic cholangiocarcinoma (iCCA), coexpressed mRNAs of DELs in iCCA tissues were significantly enriched in the PPAR signaling pathway, and KEGG enrichment of DEL target genes was demonstrated in papillary thyroid carcinoma [62,63].…”