Homeodomain-containing gene 10 contributed to breast cancer malignant behaviors by activating Interleukin-6/Janus kinase 2/Signal transducer and activator of transcription 3 pathway

Bioengineered. 2022 Jan;13(1):1335-1345. doi: 10.1080/21655979.2021.2016088.

Abstract

Homeodomain‑containing gene 10 (HOXC10) has been identified as an oncogene in various malignancies. Nevertheless, the role and function of HOXC10 in breast cancer (BC) remain unclear. RT-qPCR and Western blot were used to detect the mRNA and protein levels of genes, respectively. CCK-8, transwell, and TUNEL assays were performed to evaluate cell viability, invasion, migration, and apoptosis of BC cells in vitro. The xenograft model was established to examine the effect of HOXC10 on tumor growth in vivo. Our results indicated that HOXC10 expression was increased in BC and correlated with an unsatisfactory prognosis. Functional assays indicated that HOXC10 overexpression promoted cell proliferation and metastasis, and suppressed cell apoptosis of BC, while HOXC10 knockdown showed opposite trends. Furthermore, in vitro and in vivo assays uncovered that HOXC10 promoted the tumorigenesis of BC via the activation of IL-6/JAK2/STAT3 signaling. Overall, our study revealed that HOXC10 could function as a tumor promotor in BC by upregulating IL-6 levels to activate the JAK2/STAT3 signaling pathway.

Keywords: HOXC10; IL-6; JAK2/STAT3 pathway; breast cancer.

MeSH terms

  • Animals
  • Apoptosis
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism*
  • Humans
  • Interleukin-6 / metabolism*
  • Janus Kinase 2 / metabolism*
  • MCF-7 Cells
  • Mice
  • Neoplasm Staging
  • Neoplasm Transplantation
  • Prognosis
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction
  • Up-Regulation

Substances

  • HOXC10 protein, human
  • Homeodomain Proteins
  • IL6 protein, human
  • Interleukin-6
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • JAK2 protein, human
  • Janus Kinase 2

Grants and funding

The author(s) reported there is no funding associated with the work featured in this article.