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

• Published in: Molecular therapy. Nucleic acids Vol. 16; pp. 63 - 72
• Main Authors: Lee, Dong Hun, Kim, Ki Cheon, Hwang, Chul Ju, Park, Kyung Ran, Jung, Young Suk, Kim, Sun Young, Kim, Ji Young, Song, Ju Kyung, Song, Min Ji, Choi, Min Ki, Hwang, Dae Youn, Han, Sang-Bae, Hong, Jin Tae
• Format: Journal Article
• Language: English
• Published: United States Elsevier Limited 07.06.2019; American Society of Gene & Cell Therapy; Elsevier
• Subjects: Alzheimer's disease; Amyloid precursor protein; Cell growth; Chitinase; Data analysis; Ethyl carbamate; Gene expression; Kinases; Lung cancer; Melanoma; Presenilin; Proteins; Rodents; Software; Stat3 protein; Transcription; Transgenic mice; Tumors; Up-regulation; chitinase-3-like-1; lung tumor development; miRNA342-3p; STAT3
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1016/j.omtn.2019.02.007

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.