Scholarlink

<p>Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide, and its progression is closely linked to the establishment of an immunosuppressive tumor microenvironment. Myristoylated alanine-rich C kinase substrate (MARCKS) has been implicated in tumor biology; however, its role in regulating immune interactions in HCC remains poorly defined. Here, we performed an integrated multi-omics analysis combining bulk transcriptomics, single-cell RNA sequencing, and spatial transcriptomics to systematically investigate the expression pattern and functional relevance of MARCKS in HCC. We found that MARCKS was significantly upregulated in HCC tissues and that high MARCKS expression was associated with aggressive clinicopathological features and unfavorable prognosis. Single-cell and spatial analyses revealed that MARCKS expression was enriched in myeloid cell populations within the tumor microenvironment. Functional annotation and mIF(Multiple immunofluorescence) validation demonstrated that MARCKS expression was associated with enhanced JAK/STAT3 signaling and M2-like macrophage polarization. Consistently, MARCKS silencing in HCC cell lines reduced STAT3 phosphorylation, suppressed malignant phenotypes in vitro, inhibited tumor growth in vivo, and diminished the capacity of tumor-derived conditioned media to promote macrophage M2 polarization. Together, these findings identify MARCKS as a key regulator of the immunosuppressive tumor microenvironment in HCC and highlight its potential as a therapeutic target for overcoming immune evasion.</p><p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Integrated multi-omics analysis reveals that MARCKS reprograms the immunosuppressive microenvironment to drive hepatocellular carcinoma progression

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月11日

查看全文
  • Haifei Qin,
  • Qinchen Lu,
  • Baicheng Hu,
  • Xin Zhou,
  • Chenlu Lan,
  • Honglong Lu,
  • Donghua Gao,
  • Chongjiu Qin,
  • Kai Peng,
  • Yongguang Wei,
  • Xiwen Liao,
  • Tao Peng,
  • Liming Shang,
  • Guangzhi Zhu

摘要

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide, and its progression is closely linked to the establishment of an immunosuppressive tumor microenvironment. Myristoylated alanine-rich C kinase substrate (MARCKS) has been implicated in tumor biology; however, its role in regulating immune interactions in HCC remains poorly defined. Here, we performed an integrated multi-omics analysis combining bulk transcriptomics, single-cell RNA sequencing, and spatial transcriptomics to systematically investigate the expression pattern and functional relevance of MARCKS in HCC. We found that MARCKS was significantly upregulated in HCC tissues and that high MARCKS expression was associated with aggressive clinicopathological features and unfavorable prognosis. Single-cell and spatial analyses revealed that MARCKS expression was enriched in myeloid cell populations within the tumor microenvironment. Functional annotation and mIF(Multiple immunofluorescence) validation demonstrated that MARCKS expression was associated with enhanced JAK/STAT3 signaling and M2-like macrophage polarization. Consistently, MARCKS silencing in HCC cell lines reduced STAT3 phosphorylation, suppressed malignant phenotypes in vitro, inhibited tumor growth in vivo, and diminished the capacity of tumor-derived conditioned media to promote macrophage M2 polarization. Together, these findings identify MARCKS as a key regulator of the immunosuppressive tumor microenvironment in HCC and highlight its potential as a therapeutic target for overcoming immune evasion.