# Multi-Scale Transcriptomic Sequencing Data Analysis Reveals LINC00467 is Associated with Malignant Progression in Breast Cancer: An In Silico and In Vitro Study

## TL;DR

This study finds that LINC00467, a long non-coding RNA, is linked to breast cancer progression and drug resistance, suggesting it could be a new treatment target.

## Contribution

The study identifies LINC00467 as a novel regulator of breast cancer stemness and drug sensitivity through in silico and in vitro analyses.

## Key findings

- LINC00467 is upregulated in multiple breast cancer subtypes and is spatially specific.
- Silencing LINC00467 reduces cancer stemness and downregulates LIN28B and p-AKT.
- High LINC00467 expression correlates with reduced sensitivity to AKT inhibitors and PD-1 antibodies.

## Abstract

Long non-coding RNAs have been found to play a pivotal role in breast cancer, yet the majority of these lncRNAs remain to be thoroughly investigated. This study aimed to explore the role of differentially expressed long non-coding RNAs (lncRNAs) in breast cancer stemness and drug sensitivity.

Database mining was performed to evaluate the expression of LINC00467 in different types of breast cancer and its association with clinical features. The function of LINC00467 was examined through colony formation assays, quantitative reverse transcription PCR (qRT-PCR), and western blotting following LINC00467 silencing in breast cancer cell lines.

LINC00467 was significantly upregulated in various breast cancer subtypes with spatial specificity. Silencing LINC00467 reduced clonogenic capacity and downregulated the stemness-associated factor LIN28B as well as phosphorylated RAC-alpha serine/threonine-protein kinase (p-AKT). The transcription factors specificity protein 1 (SP1) and E2F transcription factor 1 (E2F1) were predicted to bind to the LINC00467 promoter. Furthermore, breast cancer samples with high LINC00467 expression displayed reduced sensitivity to AKT inhibitors, and high LINC00467 expression was negatively correlated with the therapeutic response to programmed cell death 1 (PD-1) antibodies.

Our findings suggest that spatially expressed LINC00467 may promote breast cancer stemness by regulating AKT signaling and could serve as a potential new therapeutic target and indicator of drug sensitivity in breast cancer.