Original Article
Downregulation of HSPA2 inhibits proliferation via ERK1/2 pathway and endoplasmic reticular stress in lung adenocarcinoma
Abstract
Background: To explore the mechanisms of HSPA2 downregulation in inhibiting the proliferation of lung adenocarcinoma.
Methods: We obtained 85 specimens of human lung adenocarcinoma and specimens of adjacent nontumor tissues from the First Affiliated Hospital, School of Medicine, Zhejiang University. We then analyzed the expression of HSPA2 in these tissues and in lung adenocarcinoma and normal lung cell lines. Human lung adenocarcinoma cell lines were transfected with siRNA silencing HSPA2 and subjected to colony forming, Thiazolyl blue tetrazolium bromide (MTT), propidium iodide flow cytometry, immunofluorescence assay and western blotting to explore the causes of the reduction in the proliferation of lung adenocarcinoma cells and the endoplasmic reticulum stress induced by HSPA2 downregulation. Finally, we confirmed these mechanisms via rescue assay.
Results: Greater HSPA2 expression was found in the lung adenocarcinoma specimens than in the specimens of adjacent nontumor tissues, and greater expression was found in lung adenocarcinoma cell lines than in normal cell lines. HSPA2 knockdown via siRNA reduced proliferation and led to G1/S phase cell cycle arrest in the lung adenocarcinoma cell lines. G1/S phase cell cycle arrest triggered by HSPA2 downregulation could be attributed, at least in part, to phosphorylation and activation of the Erk1/2 pathway and probably to activation of IRE1α/PERK-mediated endoplasmic reticulum stress.
Conclusions: HSPA2 plays an important role in the origin and development of lung adenocarcinoma. It is thus deserving of further study as a promising clinical therapeutic target.
Methods: We obtained 85 specimens of human lung adenocarcinoma and specimens of adjacent nontumor tissues from the First Affiliated Hospital, School of Medicine, Zhejiang University. We then analyzed the expression of HSPA2 in these tissues and in lung adenocarcinoma and normal lung cell lines. Human lung adenocarcinoma cell lines were transfected with siRNA silencing HSPA2 and subjected to colony forming, Thiazolyl blue tetrazolium bromide (MTT), propidium iodide flow cytometry, immunofluorescence assay and western blotting to explore the causes of the reduction in the proliferation of lung adenocarcinoma cells and the endoplasmic reticulum stress induced by HSPA2 downregulation. Finally, we confirmed these mechanisms via rescue assay.
Results: Greater HSPA2 expression was found in the lung adenocarcinoma specimens than in the specimens of adjacent nontumor tissues, and greater expression was found in lung adenocarcinoma cell lines than in normal cell lines. HSPA2 knockdown via siRNA reduced proliferation and led to G1/S phase cell cycle arrest in the lung adenocarcinoma cell lines. G1/S phase cell cycle arrest triggered by HSPA2 downregulation could be attributed, at least in part, to phosphorylation and activation of the Erk1/2 pathway and probably to activation of IRE1α/PERK-mediated endoplasmic reticulum stress.
Conclusions: HSPA2 plays an important role in the origin and development of lung adenocarcinoma. It is thus deserving of further study as a promising clinical therapeutic target.
