Tumor‐derived exosomal miR‐19b‐3p facilitates M2 macrophage polarization and exosomal LINC00273 secretion to promote lung adenocarcinoma metastasis via Hippo pathway

Clinical and Translational Medicine

卷:11

Yingru Zhi¹  Jing Chen²  Baoan Chen²  Jinyu Bai³  Xuerong Wang⁴  Kai Zhang⁵  Yin Wu⁶ 

[1] Department of Gastroenterology Nanjing First Hospital Nanjing Medical University Nanjing Jiangsu P. R. China;

[2] Department of Hematology and Oncology Zhongda Hospital, School of Medicine Southeast University Nanjing Jiangsu P. R. China;

[3] Department of Orthopedics The Second Affiliated Hospital of Soochow University Suzhou Jiangsu P. R. China;

[4] Department of Pharmacology Nanjing Medical University Nanjing Jiangsu P. R. China;

[5] Department of Respiratory Medicine Nanjing First Hospital Nanjing Medical University Nanjing Jiangsu P. R. China;

[6] Department of Respiratory Zhongda Hospital Southeast University Nanjing Jiangsu P. R. China;

关键词: exosome;    hippo signaling pathway;    lung adenocarcinoma;    M2 macrophage polarization;    miR‐19b‐3p;   

DOI  :  10.1002/ctm2.478

来源: DOAJ

【 摘 要 】

Abstract Numerous reports have elucidated the important participation of exosomes in the communication between tumor cells and other cancer‐related cells including tumor‐associated macrophages (TAMs) in microenvironment. However, the interchange of exosomes between tumor cells and TAMs in the progression of lung adenocarcinoma (LUAD) remains largely enigmatic. Herein, we discovered that LUAD cells induced the M2 polarization of TAMs and the M2‐polarized macrophages facilitated LUAD cell invasion and migration and tumor metastasis in vivo. In detail, LUAD cells secreted exosomes to transport miR‐19b‐3p into TAMs so that miR‐19b‐3p targeted PTPRD and inhibited the PTPRD‐mediated dephosphorylation of STAT3 in TAMs, leading to STAT3 activation and M2 polarization. Also, the activated STAT3 transcriptionally induced LINC00273 in M2 macrophages and exosomal LINC00273 was transferred into LUAD cells. In LUAD cells, LINC00273 recruited NEDD4 to facilitate LATS2 ubiquitination and degradation, so that the Hippo pathway was inactivated and YAP induced the transcription of RBMX. RBMX bound to miR‐19b‐3p to facilitate the packaging of miR‐19b‐3p into LUAD cell‐derived exosomes. Collectively, our results revealed the mechanism underlying the interactive communication between LUAD cells and TAMs through elucidating the exchange of exosomal miR‐19b‐3p and LINC00273 and proved the prometastatic effect of the interchange between two cells. These discoveries opened a new vision for developing LUAD treatment.

【 授权许可】

Unknown