# LncRNA SNHG4 Regulates Lipid Metabolism and Inflammation in Non-Alcoholic Fatty Liver Disease by Targeting miR-34b-5p/XIAP Axis

**Authors:** YanJu Ding, Sheng Zheng, Xin Nian Fu, Chi Ma, Yang Juan

PMC · DOI: 10.5152/tjg.2025.24191 · The Turkish Journal of Gastroenterology · 2025-05-05

## TL;DR

This study shows that the lncRNA SNHG4 helps control fat metabolism and inflammation in non-alcoholic fatty liver disease by interacting with miR-34b-5p and XIAP.

## Contribution

The novel finding is that SNHG4 regulates lipid metabolism and inflammation in NAFLD via the miR-34b-5p/XIAP axis.

## Key findings

- FFA reduced SNHG4 and XIAP but increased miR-34b-5p, causing lipid and inflammatory issues.
- Overexpression of SNHG4 reduced FFA-induced lipid and inflammatory effects, which were reversed by XIAP silencing.
- SNHG4 knockdown worsened FFA effects, but inhibiting miR-34b-5p rescued these effects.

## Abstract

This research aimed at probing the mechanism of long non-coding RNA small nucleolar RNA host gene 4 (SNHG4) in regulating lipid metabolism and inflammation in non-alcoholic fatty liver disease (NAFLD).

L02 and THLE-2 cells were stimulated with free fatty acids (FFA) and transfected. Lipid accumulation was detected through Oil Red O staining, measurements of triglyceride and total cholesterol were taken, and the levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 were assessed using enzyme-linked immunosorbent assays. The assessment of gene expression was conducted using real-time reverse transcriptase-polymerase chain reaction and Western blot techniques. The interplay between SNHG4 and miR-34b-5p/X-linked inhibitor of apoptosis protein (XIAP) was evaluated.

Free fatty acids downregulated SNHG4 and XIAP and upregulated miR-34b-5p in L02 and THLE-2 cells, leading to lipid metabolism disorder and inflammation. SNHG4 overexpression mitigated the lipid metabolism disorder and inflammation triggered by FFA, while this effect was suppressed by silencing XIAP. In contrast, SNHG4 knockdown aggravated FFA-induced lipid metabolic and inflammatory disorders, whilst this effect was rescued by inhibiting miR-34b-5p.

SNHG4 regulates lipid metabolism and inflammatory disorders in NAFLD by targeting the miR-34b-5p/XIAP axis.

## Linked entities

- **Genes:** SNHG4 (small nucleolar RNA host gene 4) [NCBI Gene 724102], XIAP (X-linked inhibitor of apoptosis) [NCBI Gene 331]
- **Proteins:** IL6 (interleukin 6), XIAP (X-linked inhibitor of apoptosis)
- **Chemicals:** triglyceride (PubChem CID 5460048)
- **Diseases:** non-alcoholic fatty liver disease (MONDO:0013209)

## Full-text entities

- **Genes:** XIAP (X-linked inhibitor of apoptosis) [NCBI Gene 331] {aka API3, BIRC4, IAP-3, ILP1, MIHA, XLP2}, SNHG4 (small nucleolar RNA host gene 4) [NCBI Gene 724102] {aka NCRNA00059, U19H}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}
- **Diseases:** lipid metabolism disorder (MESH:D052439), NAFLD (MESH:D065626), Inflammation (MESH:D007249)
- **Chemicals:** Oil Red O (MESH:C011049), cholesterol (MESH:D002784), Lipid (MESH:D008055), triglyceride (MESH:D014280), FFA (MESH:D005230)
- **Cell lines:** THLE-2 — Homo sapiens (Human), Transformed cell line (CVCL_3803), L02 — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_6926)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12520139/full.md

## References

33 references — full list in the complete paper: https://tomesphere.com/paper/PMC12520139/full.md

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Source: https://tomesphere.com/paper/PMC12520139