Abstract
Background
Long non-coding RNAs (lncRNAs) is widely described as a class of RNA longer than 200 nucleotides without encoding capability. But recent years, more and more open reading frames (ORFs) have been found in lncRNAs which indicate they have coding capacity. But the mechanisms of the encoding products in cancer are mostly unknown. We have previously shown lncRNA HCP5 is an oncogene in triple negative breast cancer (TNBC), and the aim of the current study was to investigate if lncRNA HCP5 encoding protein promotes TNBC by regulating ferroptosis.
Methods
We use bioinformatics to predict coding capacity. Molecular biology experiments and the xenograft assay in nude mice to study the mechanism of lncRNA HCP5 encoding protein. And the protein expression was evaluated in a tissue microarray of 140 invasive breast tumors and 45 pared precancerous breast tissues. Association between the protein expression and clinicopathologic features of breast cancer patients was analyzed.
Results
In this study, we identify that ORF in lncRNA HCP5 can encode a conserved protein with 132-amino acid. The protein, which is named HCP5-132aa, promotes TNBC growth. Mechanistically, the HCP5-132aa regulates GPX4 expression and lipid ROS level through ferroptosis pathway to promote TNBC progression. HCP5-132aa ORF knockdown synergizes with ferroptosis activators in vitro and in vivo. Breast cancer patients with high levels of HCP5-132aa have poorer prognosis.
Conclusions
Our study indicates that overexpression of lncRNA HCP5 encoding protein is a critical oncogenic event in TNBC. Our findings uncover a regulatory mechanism of ferroptosis in TNBC orchestrated by a protein encoded by an lncRNA.
High ERK Protein Expression Levels Correlate with Shorter Survival in Triple‐Negative Breast Cancer Patients
