Vorinostat triggers miR-769–5p/3p-mediated suppression of proliferation and induces apoptosis via the STAT3-IGF1R-HDAC3 complex in human gastric cancer. (28th November 2021)

• Record Type: Journal Article
• Authors: Dai, Weiyu; Liu, Side; Zhang, Jieming; Pei, Miaomiao; Xiao, Yizhi; Li, Jiaying; Hong, Linjie; Lin, Jianjiao; Wang, Jing; Wu, Xiaosheng; Liu, Guangnan; Chen, Yaying; Wang, Yusi; Lin, Zhizhao; Yang, Qiong; Zhi, Fachao; Li, Guoxin; Tang, Weimei; Li, Aimin; Xiang, Li; Wang, Jide
• Is Part Of: Cancer letters. Volume 521(2021)
• Page Start: 196
• Page End: 209
• Publication Date: 2021-11-28
• Subjects: microRNAs -- Histone deacetylase inhibitors -- Cell growth -- Transcription; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2021.09.001
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Previous reports have shown that histone deacetylase inhibitors (HDACi) can alter miRNA expression in a range of cancers. Both the 5p-arm and 3p-arm of mature miRNAs can be expressed from the same precursor and involved in cancer progress. Nevertheless, the detailed mechanism by which vorinostat (SAHA), a HDACi, triggers miR-769–5p/miR-769-3p-mediated suppression of proliferation and induces apoptosis in gastric cancer (GC) cells remains elusive. Here, we showed that the miRNA-seq analysis of GC cells treated with SAHA identified seven differentially expressed miRNAs with both strands of the miRNA duplex. miR-769–5p/miR-769–3p expression was downregulated in GC tissues compared with normal tissues. Functionally, high expression of miR-769–5p/miR-769–3p blocked the malignant abilities of GC cells. Mechanistically, miR-769–5p/miR-769–3p targeted IGF1R and IGF1R overexpression rescued the effects of miR-769–5p/miR-769–3p on GC cells growth and metastasis. Moreover, STAT3 bound to the promoter of miR-769. Furthermore, miR-769–5p/miR-769–3p expression was negatively regulated by the STAT3-IGF1R-HDAC3 complex. Besides, miR-769–5p/miR-769–3p synergized with SAHA to promote GC cells apoptosis. Our studies suggest that miR-769–5p/miR-769–3p acts as a tumor suppressor by the STAT3-IGF1R-HDAC3 complex. Moreover, SAHA triggers miR-769–5p/miR-769-3p-mediated inhibition of proliferation and induces apoptosis in GC cells. Highlights: Vorinostat (SAHA) upregulates miR-769–5p/3p in gastric cancer (GC) cells. miR-769–5p/3p attenuates the malignant biological behavior of GC. miR-769–5p/3p is negatively regulated by the STAT3-IGF1R-HDAC3 complex in GC. SAHA synergizes with miR-769–5p/3p to trigger apoptosis in GC cells.