Znhit1 inhibits breast cancer by up-regulating PTEN to deactivate the PI3K/Akt/mTOR pathway.

Abstract

AIMS\nBreast cancer (BC) is the most frequently diagnosed cancer, ranking sixth as the cause of death among females in China. Zinc finger HIT-type containing 1 (Znhit1) is a pivotal factor for inhibition of gene mutation and cell proliferation. Due to the unknown function of Znhit1 in cancers, we aimed to explore the role of Znhit1 in BC as well as the underlying mechanisms.\n\n\nMAIN METHODS\nZnhit1 expression in clinical specimens and cell lines of BC was measured by quantitative reverse transcription PCR and Western blot analysis. Then, the effects of Znhit1 overexpression on cell proliferation, apoptosis and invasion of BC cells as well as in vivo tumor growth were assessed. The interactions among Znhit1, PTEN and the downstream PI3K/Akt/mTOR pathway were evaluated by Western blot analysis. Finally, the role of Znhit1 in prognosis was analyzed in clinical specimens.\n\n\nKEY FINDINGS\nZnhit1 was down-regulated in BC cell lines and clinical specimens. Znhit1 overexpression induced apoptosis and repressed proliferation and invasion of BC cells. Moreover, Znhit1 overexpression induced cell cycle arrest at G0/G1 stage. In vivo data showed that Znhit1 overexpression inhibited BC tumor growth in mice. Further experiments showed Znhit1 affected BC through up-regulating PTEN, along with inactivation of the PI3K/Akt/mTOR pathway. We finally proved that high expression of Znhit1 indicated improved prognosis.\n\n\nSIGNIFICANCE\nZnhit1 overexpression inhibited BC tumorigenesis possibly through PTEN-mediated inactivation of the PI3K/Akt/mTOR pathway. Additionally, high expression of Znhit1 indicated improved prognosis.