Decreased Lung Tumor Development in SwAPP Mice through the Downregulation of CHI3L1 and STAT 3 Activity via the Upregulation of miRNA342-3p.

ABSTRACT

We previously found that lung tumor development was reduced in a presenilin (PS) Alzheimer's disease (AD) mouse model. Here, we investigated whether this reducing effect could occur in a different AD mouse model. We investigated urethane-induced (1 mg/g) lung tumor development and melanoma growth in Swedish amyloid precursor protein (SwAPP) transgenic mice. The expression of chitinase-3-like-1 (Chi3L1) increased during lung tumor development and melanoma growth, which was accompanied by an increase in the activity of signal transducer and activator of transcription 3 (STAT3) and the downregulation of miRNA342-3p in wild-type mice. Like tumor development, the expression of Chi3L1 and STAT3 activity was reduced in the SwAPP mice, whereas the expression of miRNA342-3p was upregulated. In addition, Chi3L1 knockdown in the lung cancer and melanoma tissues reduced cancer cell growth and STAT3 activity but enhanced miRNA342-3p expression. However, the miRNA342-3p mimic decreased Chi3L1 expression, cancer cell growth, and STAT3 activity. Moreover, a STAT3 inhibitor reduced Chi3L1 expression and cancer cell growth but enhanced miRNA342-3p expression. These data showed that lung tumor development was reduced through the decrease of Chi3L1 expression via the STAT3-dependent upregulation of miRNA342-3p. This study indicates that lung tumor development could be reduced in SwAPP AD mice.