# Unveiling the oncogenic role of lncRNA PIG13-DT in hepatocellular carcinoma progression

## TL;DR

This study reveals that the lncRNA PIG13-DT promotes liver cancer progression by interacting with YBX3 and USP15, offering potential for new treatments.

## Contribution

The study identifies a novel PIG13-DT/YBX3/USP15 axis in hepatocellular carcinoma progression.

## Key findings

- PIG13-DT is highly expressed in HCC tissues and linked to poor prognosis.
- PIG13-DT enhances cancer stem cell function and promotes tumor cell proliferation and migration.
- PIG13-DT stabilizes YBX3 and promotes USP15 mRNA translation, driving HCC progression.

## Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality due to delayed diagnosis and poor prognosis. Long non-coding RNAs (lncRNAs) are key cancer regulators, yet the role of C1orf21-DT (PIG13-DT) in HCC remains unclear.

We evaluated PIG13-DT expression in HCC and paired adjacent non-tumorous tissues. Functional studies were conducted using cell culture, cell-derived xenotransplantation (CDX) models, and molecular techniques including RNA pull-down, mass spectrometry, RIP-qPCR, and RNA sequencing. We explored the interplay between PIG13-DT, RNA-binding protein YBX3, and USP15 mRNA.

PIG13-DT was highly expressed in HCC tissues compared with normal tissues and associated with poor prognosis. Functionally, PIG13-DT enhanced cancer stem cell (CSC) function, reduced reactive oxygen species (ROS) levels, and promoted HCC cell proliferation and migration. Mechanistically, PIG13-DT interacted with YBX3, stabilizing YBX3 and promoting USP15 mRNA translation and stability, thus driving HCC progression. Clinical data from lenvatinib-treated HCC patients showed that PIG13-DT expression was correlated with poor treatment response.

Our study identifies a novel PIG13-DT/YBX3/USP15 axis driving HCC progression, suggesting PIG13-DT as a potential biomarker and therapeutic target. This work provides new insights into HCC molecular mechanisms and offers potential diagnostic and therapeutic implications.