Bioinformatic identification of genomic instability-associated lncRNAs signatures for improving the clinical outcome of cervical cancer by a prognostic model

Abstract

The research is executed to analyze the connection between genomic instability-associated long non-coding RNAs (lncRNAs) and the prognosis of cervical cancer patients. We set a prognostic model up and explored different risk groups' features. The clinical datasets and gene expression profiles of 307 patients have been downloaded from The Cancer Genome Atlas database. We established a prognostic model that combined somatic mutation profiles and lncRNA expression profiles in a tumor genome and identified 35 genomic instability-associated lncRNAs in cervical cancer as a case study. We then stratified patients into low-risk and high-risk groups and were further checked in multiple independent patient cohorts. Patients were separated into two sets: the testing set and the training set. The prognostic model was built using three genomic instability-associated lncRNAs (AC107464.2, MIR100HG, and AP001527.2). Patients in the training set were divided into the high-risk group with shorter overall survival and the low-risk group with longer overall survival (p < 0.001); in the meantime, similar comparable results were found in the testing set (p = 0.046), whole set (p < 0.001). There are also significant differences in patients with histological grades, FIGO stages, and different ages (p < 0.05). The prognostic model focused on genomic instability-associated lncRNAs could predict the prognosis of cervical cancer patients, paving the way for further research into the function and resource of lncRNAs, as well as a key approach to customizing individual care decision-making.

Effects of BRD4 inhibitor JQ1 on the expression profile of super-enhancer related lncRNAs and mRNAs in cervical cancer HeLa cells

“…Current evidence revealed that lncRNAs have important regulatory roles in the cancer biology of CC ( Aalijahan & Ghorbian, 2019 ; He et al, 2020 ; Shi, Zhang & Liu, 2018a ; Zhang et al, 2021a ). Thus, this theoretical basis inspired our speculation that JQ1 might regulate the expression of target genes through lncRNAs to control the malignant behavior of Hela cells.…”

LncmiRHG-MIR100HG: A new budding star in cancer

“…Papillomavirus infection is a major causative factor for CACX in high-risk populations, and the long latency period for tumor development after the infection has other genetic and epigenetic changes that lead to deregulation of cellular pathways, which in turn affect protein-coding genes and non-protein-coding genes (75). MIR100HG was found significantly differentially expressed and down-regulated in CACX (53) and CACX patients with pelvic lymph node metastasis (PLNM) (21), and pathway analysis showed a significant correlation with the "cell growth and proliferation" and "cancer" phenotypes (54). Zhang et al (53) established a prognostic model of CACX with genomic instability-associated lncRNAs including MIR100HG, AC107464.2, and AP001527.2.…”

“…MIR100HG was found significantly differentially expressed and down-regulated in CACX (53) and CACX patients with pelvic lymph node metastasis (PLNM) (21), and pathway analysis showed a significant correlation with the "cell growth and proliferation" and "cancer" phenotypes (54). Zhang et al (53) established a prognostic model of CACX with genomic instability-associated lncRNAs including MIR100HG, AC107464.2, and AP001527.2. Besides, the biological function of MIR100HG was correlated with promoter methylation of CACX.…”

LncRNA LINC00649 aggravates the progression of cervical cancer through sponging miR‐216a‐3p

“…A recent study reported genomic instability-associated lncRNAs signatures from the Cancer Genome Atlas database in cervical cancer, among which include LINC00649. 15 Herein, the physiological function and clinical significance of LINC00649 in cervical cancer remain unclear. Firstly, the expression of LINC00649 in tumor tissues was detected and its clinical potential role was explored.…”

“…However, its role in other types of cancer has not been studied. A recent study reported genomic instability‐associated lncRNAs signatures from the Cancer Genome Atlas database in cervical cancer, among which include LINC00649 15 . Herein, the physiological function and clinical significance of LINC00649 in cervical cancer remain unclear.…”