Exosome-mediated transfer of SNHG7 enhances docetaxel resistance in lung adenocarcinoma. (1st February 2022)

• Record Type: Journal Article
• Authors: Zhang, Kai; Chen, Jing; Li, Chen; Yuan, Yuan; Fang, Surong; Liu, Wenfei; Qian, Yingying; Ma, Jiyong; Chang, Ligong; Chen, Feifei; Yang, Zhenhua; Gu, Wei
• Is Part Of: Cancer letters. Volume 526(2022)
• Page Start: 142
• Page End: 154
• Publication Date: 2022-02-01
• Subjects: Chemoresistance -- Macrophage M2 polarization -- Autophagy -- ATG5 -- PI3K/AKT pathway; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2021.10.029
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Long noncoding RNA (lncRNA) small nucleolar RNA host gene 7 (SNHG7) has been widely reported in various cancers, including lung adenocarcinoma (LUAD). However, it is largely unknown whether SNHG7 is involved in docetaxel resistance of LUAD. In the current study, we identified the high expression of SNHG7 in docetaxel-resistant cells. Through functional assays, we determined that silencing of SNHG7 decreased IC50 value of LUAD cells to docetaxel and suppressed proliferation and autophagy in LUAD cells, and reversed M2 polarization in macrophages. Mechanistically, we uncovered that SNHG7 promoted autophagy via recruiting human antigen R (HuR) to stabilize autophagy-related genes autophagy related 5 (ATG5) and autophagy related 12 (ATG12). Moreover, exosomal SNHG7 was transmitted from docetaxel-resistant LUAD cells to parental LUAD cells and thus facilitated docetaxel resistance. Additionally, exosomal SNHG7 activated the phosphatidylinositol 3-kinase (PI3K)/AKT pathway to promote M2 polarization in macrophages via recruiting cullin 4A (CUL4A) to induce ubiquitination and degradation of phosphatase and tensin homolog (PTEN). Taken together, we concluded that exosomal SNHG7 enhances docetaxel resistance of LUAD cells through inducing autophagy and macrophage M2 polarization. All findings in the study suggested that SNHG7 may be a promising target for relieving docetaxel resistance in LUAD. Highlights: SNHG7 enhances the resistance of docetaxel in LUAD. SNHG7 induces autophagy-associated docetaxel resistance of LUAD cells via regulating ATG5 and ATG12. Exosomal SNHG7 promotes docetaxel resistance of LUAD cells and macrophages M2 polarization. SNHG7 activates PI3K/AKT pathway to mediate macrophages M2 polarization via inducing PTEN ubiquitination.