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RNA-Seq Technology Reveals the Mechanism of SDT Combined With Novel Nanobubbles Against HCC.

ABSTRACT: Sonodynamic therapy is widely used in the treatment and research of hepatocellular carcinoma. A novel targeted nanobubble complex mediated with Hematoporphyrin monomethyl ether and Lonidamine was structured as a sensitizer, characterized the properties, and studied the therapeutic effect on hepatocellular carcinoma. The complexes can promote the apoptosis of hepatocellular carcinoma cells and work better in combination with sonodynamic therapy. The differential expression of multiple types of RNA in hepatocellular carcinoma with sonodynamic therapy can be identified accurately with high-throughput RNA sequencing. The differential expressions of mRNA, lncRNA, and circRNA were analyzed by RNA-Seq. The enrichment analyses (Gene Ontology and KEGG) prompted the meaningful genes and pathways in the process of sonodynamic therapy in hepatocellular carcinoma cells. HMME-LND@C₃F₈-NBs conjugated with ultrasound is confirmed efficiently for inhibiting the development of hepatocellular carcinoma cells, and it is a combination of multiple genes and mechanisms.

SUBMITTER: Shang H

PROVIDER: S-EPMC8859324 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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RNA-Seq Technology Reveals the Mechanism of SDT Combined With Novel Nanobubbles Against HCC.

Shang Haitao H Chen Yichi Y Wang Chunyue C Zhang Shentao S Wu Bolin B Liang Xitian X Liu Zhao Z Wang Qiucheng Q Cheng Wen W

Frontiers in molecular biosciences 20220207

Sonodynamic therapy is widely used in the treatment and research of hepatocellular carcinoma. A novel targeted nanobubble complex mediated with Hematoporphyrin monomethyl ether and Lonidamine was structured as a sensitizer, characterized the properties, and studied the therapeutic effect on hepatocellular carcinoma. The complexes can promote the apoptosis of hepatocellular carcinoma cells and work better in combination with sonodynamic therapy. The differential expression of multiple types of RN ...[more]

PMID: 35198599

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Project description:BackgroundThe combination of sonodynamic therapy and oxygenation strategy is widely used in cancer treatment. However, due to the complexity, heterogeneity and irreversible hypoxic environment produced by hepatocellular carcinoma (HCC) tissues, oxygen-enhancing sonodynamic therapy (SDT) has failed to achieve the desired results. With the emergence of ferroptosis with reactive oxygen species (ROS) cytotoxicity, this novel cell death method has attracted widespread attention.MethodsIn this study, nanobubbles (NBs) were connected with the sonosensitizer Indocyanine green (ICG) to construct a 2-in-1 nanoplatform loaded with RAS-selective lethal (RSL3, ferroptosis promoter) (RSL3@O2-ICG NBs), combined with oxygen-enhanced SDT and potent ferroptosis. In addition, nanobubbles (NBs) combined with low-frequency ultrasound (LFUS) are called ultrasound-targeted nanobubble destruction (UTND) to ensure specific drug release and improve safety.ResultsMDA/GSH and other related experimental results show that RSL3@O2-ICG NBs can enhance SDT and ferroptosis. Through RNA sequencing (RNA-seq), the differential expression of LncRNA and mRNA before and after synergistic treatment was identified, and then GO and KEGG pathways were used to enrich and analyze target genes and pathways related ferroptosis sensitivity. We found that they were significantly enriched in the ferroptosis-related pathway MAPK cascade and cell proliferation. Then, we searched for the expression of differentially expressed genes in the TCGA Hepatocellular carcinoma cohort. At the same time, we evaluated the proportion of immune cell infiltration and the identification of co-expression network modules and related prognostic analysis. We found that it was significantly related to the tumor microenvironment of hepatocellular carcinoma. The prognostic risk genes "SLC37A2" and "ITGB7" may represent new hepatocellular carcinoma ferroptosis-inducing markers and have guiding significance for treating hepatocellular carcinoma.ConclusionThe therapeutic effect of the in vitro synergistic treatment has been proven to be significant, revealing the prospect of 2-in-1 nanobubbles combined with SDT and ferroptosis in treating HCC.

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RNA-Seq Technology Reveals the Mechanism of SDT Combined With Novel Nanobubbles Against HCC.

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RNA-Seq Technology Reveals the Mechanism of SDT Combined With Novel Nanobubbles Against HCC.

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