Expression profiling of long noncoding RNA in human uterine leiomyoma

Abstract

Objective To investigate the differential expression profiles of long non-coding RNA (lncRNA) in uterine leiomyoma (ULM) and adjacent normal myometrium tissues, explore the role of lncRNA in the pathogenesis of uterine leiomyoma. Methods Tissue samples of 41 patients with ULM who underwent hysterectomy in Henan People’s Hospital from April 2017 to September 2018 were collected. 1) SBC-ceRNA high throughput microarray technology was performed to identify the differential expression profiles of lncRNA in five ULM tissues and paired normal myometrial tissues. 2) Bioinformatics methods (GO and KEGG) were used to analyze the biological function and regulatory signaling pathway network of the differentially expressed lncRNAs in ULM. 3) qRT-PCR assay was applied to verify the differential expression of candidate lncRNAs in 36 pairs of leiomyoma tissues and paired myometrium tissues. 4) Association of candidate lncRNA expression and clinical pathological features of ULM was evaluated. Results 1) A total of 789 differentially expressed lncRNA transcripts (412 up-regulated and 377 down-regulated) were identified between leiomyoma and adjacent myometrium tissues. 2) Enrichment analysis revealed that dysregulated transcripts were mainly involved in extracellular matrix (ECM) assembly, p53 and mTOR signaling transduction. 3) Candidate lncRNAs were selected for validation using qRT-PCR assay in extended clinical samples and demonstrated that RP11-595O22.1, CTD-3080F16.3, RP11-486F17.1, IGF2-AS were up-regulated in leiomyoma tissues (P=0.000 3, P=0.001 1, P=0.000 2, P<0.000 1), whereas RP11-253M7.1, RP11-1100L3.8 were down-regulated (P=0.000 6, P=0.011). 4) Furthermore, IGF2-AS levels were associated with leiomyoma size (P=0.043 1). Conclusion LncRNA profiles were identified and differential expression pattern conformed in ULM and paired normal myometrium counterpart. Our study provided an integrated analysis of global lncRNA profile and specific regulatory network in ULM, may give novel epigenetic insight and biomarker for further target therapy development. Key words: Uterine Leiomyoma; Long noncoding RNA; Microarray