LncRNA HCP5 Encoding Protein Regulates Ferroptosis To Promote The Progression of Triple Negative Breast Cancer

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.

Long non-coding RNA HOTAIR promotes breast cancer progression and metastasis, induces ferroptosis by regulating the miR-206/CERS2 axis

“…Shi et al [41] discovered that loss of lncRNA DUXAP8 synergistically enhances sorafenibinduced ferroptosis in hepatocellular carcinoma through SLC7A11 de-palmitoylation. Tong et al [42] demonstrated that the protein encoded by lncRNA HCP5 regulates ferroptosis to promote triplenegative breast cancer progression. In our study, we found that HOTAIR competitively binds more miR-206, leading to reduced miR-206-mediated CERS2 inhibition and thereby increasing the sensitivity of BRCA cells to ferroptosis.…”

Identification and Validation of a m5c-related lncrna signature predict prognosis and immune response of clear cell renal cell carcinoma

“…However, with the deepening of understanding, it has been found that LncRNAs are widely distributed in eukaryotes and participate in various important biological functions, including the regulation of autophagy [8], speci c transcriptional and posttranscriptional controls [9], transduction of intermolecular signals [10], and regulation of protein stability after translation [11]. In the research of cancer, LncRNAs are differentially expressed in prostate cancer, breast cancer, colorectal cancer, pancreatic cancer, non-small cell lung cancer, hepatocellular carcinoma and so on, and play an important role in the proliferation, migration and invasion of tumor cells [12][13][14][15][16][17].…”