High expression of Rab31 confers a poor prognosis and enhances cell proliferation and invasion in oral squamous cell carcinoma

Oncol Rep. 2021 Mar;45(3):1182-1192. doi: 10.3892/or.2021.7940. Epub 2021 Jan 18.

Abstract

Dysregulation of Rab proteins has been observed in various types of cancer. Ectopic expression of Rab31, a member of the Rab protein family, is involved in cancer development and progression. However, the specific role and potential molecular mechanism underlying the functions of Rab31 remain largely unknown. Therefore, the current study aimed to investigate the functions of Rab31 in the development of cancer. Human oral squamous cell carcinoma (OSCC) samples were examined to determine the expression profile of Rab31 and its association with the clinicopathological characteristics of patients with OSCC. Knockdown of Rab31 expression with short hairpin RNA was performed to analyze the functions of Rab31 in vitro and in vivo. The expression of Rab31 was significantly elevated in human OSCC samples compared with that in normal oral mucosal epithelial tissues, and high expression levels were associated with high pathological grades. Furthermore, positive expression of Rab31 was associated with a poor prognosis in patients with OSCC. In addition, knockdown of Rab31 expression suppressed OSCC cell proliferation and induced apoptosis compared with those in the control‑transfected cells, which may have been caused by downregulated cyclin D1 and survivin expression and upregulated B‑cell lymphoma 2 expression. The invasive ability of OSCC cells was also abrogated by Rab31 silencing compared with that in the control‑transfected cells, which was associated with downregulated N‑cadherin and matrix metalloproteinase‑9 expression levels and upregulated levels of E‑cadherin expression. Furthermore, silencing Rab31 in OSCC cell lines, when compared with the control‑transfected cells, significantly reduced tumor growth and inhibited the expression of survivin, Ki‑67 and N‑cadherin in vivo. By contrast, the expression levels of E‑cadherin were increased. Taken together, the results of the present study supported important roles for Rab31 in regulating OSCC cell proliferation, apoptosis and invasion and may facilitate the identification of a new therapeutic target for the treatment of OSCC.

Keywords: Rab31; oral squamous cell carcinoma; prognosis; proliferation; invasion.

Publication types

  • Observational Study

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Healthy Volunteers
  • Humans
  • Mice
  • Mouth Mucosa / pathology*
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / mortality
  • Mouth Neoplasms / pathology
  • Neoplasm Invasiveness / genetics
  • Prognosis
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / mortality
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Xenograft Model Antitumor Assays
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism*

Substances

  • RAB31 protein, human
  • rab GTP-Binding Proteins

Grants and funding

This work was supported by The National Natural Science foundation Project (grant no. 81570949), The Excellent Subject Leader Plan of Shanghai Municipal Commission of Health and Family Planning (grant no. 2017BR019), The Youth Project of Shanghai Municipal Commission of Health and Family Planning (grant no. 20164Y0067), The Science and Technology Commission of Shanghai Municipality, Natural Science Grant (grant no. 19ZR1430000) and The Hospital Innovation Project (grant no. CK2019004).