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

• Published in: Clinical and translational medicine Vol. 11; no. 9; pp. e478 - n/a
• Main Authors: Chen, Jing, Zhang, Kai, Zhi, Yingru, Wu, Yin, Chen, Baoan, Bai, Jinyu, Wang, Xuerong
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.09.2021; John Wiley and Sons Inc; Wiley
• Subjects: A549 Cells; Adenocarcinoma of Lung - genetics; Adenocarcinoma of Lung - metabolism; Cell Line, Tumor; Clinical medicine; Communication; exosome; Exosomes - metabolism; hippo signaling pathway; Hippo Signaling Pathway - genetics; Humans; Kidney cancer; Kinases; lung adenocarcinoma; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; M2 macrophage polarization; Macrophage Activation - genetics; Macrophages - metabolism; Medical research; Metastasis; MicroRNAs; miR‐19b‐3p; Phosphatase; Proteins; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Transmission electron microscopy; Tumors; United States > US; China; M2 macrophage polarization; miR-19b-3p; hippo signaling pathway; exosome; lung adenocarcinoma
• ISSN: 2001-1326; 2001-1326
• DOI: 10.1002/ctm2.478

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. LUAD cell‐derived exosomal miR‐19b‐3p induce M2 polarization in THP‐1 cells by targeting PTPRD/STAT3 and STAT3 activated LINC00273 was transmitted by M2 macrophage‐derived exosomes to LUAD cells, activating YAP to induce RBMX‐mediated packaging of miR‐19b‐3p into LUAD cell‐derived exosomes.