# Mechanistic Insights and Therapeutic Potential of Small Nucleolar RNA Host Genes in the Carcinogenesis of Hepatocellular Carcinoma

## TL;DR

This review explores how small nucleolar RNA host genes contribute to liver cancer development and their potential as diagnostic and therapeutic tools.

## Contribution

The paper provides a comprehensive overview of SNHGs' dual mechanisms (ceRNA and non-ceRNA) in HCC progression and their clinical potential.

## Key findings

- SNHGs influence HCC through mechanisms like proliferation, apoptosis, and tumor microenvironment changes.
- They contribute to drug resistance and metabolic dysregulation in HCC.
- SNHGs show promise as diagnostic markers and therapeutic targets for liver cancer.

## Abstract

Hepatocellular carcinoma (HCC) is one of the major factors endangering human health due to its poor prognosis, resulting from difficulties in early diagnosis and lack of effective treatment measures. Long non‐coding RNAs (lncRNAs), which are RNA molecules that do not translate into proteins, play essential roles in various tumor malignancy mechanisms. Among these, small nucleolar host genes (SNHGs) represent a specific subgroup of lncRNAs that have recently been shown to be critically involved in the development of HCC.

This review aims to summarize recent findings regarding the role of SNHGs in HCC carcinogenesis, and to clarify their mechanistic functions in cancer progression as well as their potential as diagnostic markers and therapeutic targets.

A comprehensive literature search was performed in the PubMed database using the following keywords: “small nucleolar host gene”, and “hepatocellular carcinoma”, or “liver cancer”. Relevant literature was retrieved and screened to synthesize the latest research findings on the roles of SNHGs in HCC carcinogenesis. No restrictions were predefined on the publication time of the included literature, and studies focusing on the mechanistic insights and therapeutic potential of SNHGs in HCC were prioritized for inclusion in this narrative review.

Abnormal expression of SNHGs in HCC affects many facets of the disease, including tumor cell proliferation, stemness, invasion, migration, apoptosis, autophagy, ferroptosis (an iron‐dependent form of cell death), and pyroptosis (a highly inflammatory form of programmed cell death), as well as metabolic processes such as glycolysis, lipid and cholesterol metabolism. Furthermore, these expressions can alter the tumor microenvironment and contribute to resistance against sorafenib, a common treatment for HCC. Numerous studies have further revealed SNHGs promote the onset and progression of HCC through competing endogenous RNA (ceRNA, different RNA molecules compete for same microRNAs) network. Additionally, recent research shows that non‐ceRNA mechanisms, including small nucleolar RNA (snoRNA) mediated regulation, epigenetic regulation, and modulation of mRNA stability, also contribute to SNHGs' regulation of HCC development and progression.

SNHGs play critical regulatory roles in HCC carcinogenesis and progression through both ceRNA and non‐ceRNA mechanisms. They hold potential as promising diagnostic markers and therapeutic targets for HCC, providing new insights for the clinical management of this disease.