Knockdown of ALPK2 blocks development and progression of renal cell carcinoma

Exp Cell Res. 2020 Jul 15;392(2):112029. doi: 10.1016/j.yexcr.2020.112029. Epub 2020 Apr 21.

Abstract

Renal cell carcinoma (RCC) is one of the most common malignant tumors in the urinary system, whose molecular mechanism is still not clear. ALPK2 is a member of alpha protein kinase family, and its relationship with RCC is never reported. In this study, expression of ALPK2 in tumor tissues or cells of RCC was detected by qPCR, western blotting and immunohistochemical analysis. The effects of ALPK2 knockdown on cell proliferation, colony formation, cell migration and apoptosis were assessed by MTT, colony formation assay, wound-healing assay, Transwell assay and flow cytometry, respectively. The influence of ALPK2 knockdown on tumor growth in vivo was evaluated by mice xenograft models. The results demonstrated that ALPK2 was upregulated in tumor tissues of RCC and its high expression was significantly associated with advanced stage and poor prognosis. Knockdown of ALPK2 could inhibited cell proliferation, colony formation and cell migration of RCC cells, while promoting cell apoptosis. The suppression of tumor growth in vivo by ALPK2 knockdown was also showed by using mice xenograft models. Moreover, the regulation of RCC by ALPK2 may involve Akt, CDK6, Cyclin D1 and PIK3CA signaling. Therefore, our studies suggested that ALPK2 may act as a tumor promotor in the development and progression of RCC, and could be considered as a novel therapeutic target for RCC treatment.

Keywords: ALPK2; Cell apoptosis; Cell migration; Cell proliferation; Renal cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology*
  • Cell Proliferation
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Prognosis
  • Protein Kinases / chemistry
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • RNA, Small Interfering / genetics
  • Survival Rate
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • RNA, Small Interfering
  • ALPK2 protein, human
  • Protein Kinases