ALDH5A1 acts as a tumour promoter and has a prognostic impact in papillary thyroid carcinoma

Cell Biochem Funct. 2021 Mar;39(2):317-325. doi: 10.1002/cbf.3584. Epub 2020 Sep 2.

Abstract

Thyroid cancer is the most common endocrine carcinoma, with papillary thyroid carcinoma (PTC) accounting for 80%-90% of thyroid cancers. Accumulating studies reported that mitochondria plays an important role in the regulation of cell proliferation. ALDH5A1, may function as an oncogene or tumour suppressor in various human cancers, and the role of ALDH5A1 in PTC is still unclear. The aim of this study was to investigate the clinical significance of ALDH5A1 expression and its functions in PTC. In this present study, we studied ALDH5A1 expression on primary papillary thyroid carcinoma (PTC) in The Cancer Genome Atlas (TCGA) database. Results showed that the levels of ALDH5A1 were found positively correlated with tumour stage, metastasis, lymph node stage, and higher levels of ALDH5A1 demonstrated poor disease-free survival (DFS). Immunohistochemistry (IHC) revealed that significantly higher expression of ALDH5A1 was found in PTC tissues. On the other hand, knockdown of ALDH5A1 significantly inhibited PTC cell proliferation, migration and invasion detection found the migration and invasion of cells also were hindered when ALDH5A1 level was reduced. The knockdown of ALDH5A1 inhibited the expression of Vimentin and promoted the expression of E-cadherin. In brief, knockdown of ALDH5A1may act as a novel molecular target for the prevention and treatment of PTC. SIGNIFICANCE OF THE STUDY: The present study focused on the role and the potential mechanism of ALDH5A1 in papillary thyroid carcinoma. We demonstrated that reduced expression of ALDH5A1 might inhibit the progression of TC by inhibiting cell proliferation, migration and invasion and reversing epithelial-mesenchymal transition (EMT). The findings ensured the interaction relation between ALDH5A1 and EMT in PTC, providing a novel biological marker for PTC and enriching the potential strategies for TC treatment.

Keywords: ALDH5A1; EMT; invasion; metastasis; papillary thyroid carcinoma.

MeSH terms

  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Neoplasm Staging
  • Prognosis
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Succinate-Semialdehyde Dehydrogenase / antagonists & inhibitors
  • Succinate-Semialdehyde Dehydrogenase / genetics
  • Succinate-Semialdehyde Dehydrogenase / metabolism*
  • Thyroid Cancer, Papillary / metabolism
  • Thyroid Cancer, Papillary / mortality
  • Thyroid Cancer, Papillary / pathology*
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / mortality
  • Thyroid Neoplasms / pathology*
  • Vimentin / metabolism

Substances

  • Cadherins
  • RNA, Small Interfering
  • Vimentin
  • ALDH5A1 protein, human
  • Succinate-Semialdehyde Dehydrogenase