Cancer-associated fibroblasts activated by miR-196a promote the migration and invasion of lung cancer cells.

Autor: Lee S; Department of Molecular Medicine, College of Medicine, Ewha Womans University, Seoul, 07804, South Korea; Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul, 07804, South Korea., Hong JH; Division of Oncology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, 06591, South Korea., Kim JS; Department of Molecular Medicine, College of Medicine, Ewha Womans University, Seoul, 07804, South Korea; Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul, 07804, South Korea., Yoon JS; Division of Oncology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, 06591, South Korea., Chun SH; Division of Oncology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, 06591, South Korea., Hong SA; Department of Pathology, College of Medicine, Chung-Ang University, Seoul, 06974, South Korea., Kim EJ; Department of Molecular Medicine, College of Medicine, Ewha Womans University, Seoul, 07804, South Korea; Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul, 07804, South Korea., Kang K; Department of Microbiology, College of Science & Technology, Dankook University, Cheonan, 31116, South Korea., Lee Kang J; Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul, 07804, South Korea; Department of Physiology, College of Medicine, Ewha Womans University, Seoul, 07804, South Korea., Ko YH; Division of Oncology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, 06591, South Korea; Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, 06591, South Korea. Electronic address: koyoonho@catholic.ac.kr., Ahn YH; Department of Molecular Medicine, College of Medicine, Ewha Womans University, Seoul, 07804, South Korea; Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul, 07804, South Korea. Electronic address: yahn@ewha.ac.kr.
Jazyk: angličtina
Zdroj: Cancer letters [Cancer Lett] 2021 Jun 28; Vol. 508, pp. 92-103. Date of Electronic Publication: 2021 Mar 26.
DOI: 10.1016/j.canlet.2021.03.021
Abstrakt: Fibroblasts in the tumor microenvironment, known as cancer-associated fibroblasts (CAFs), promote the migration, invasion, and metastasis of cancer cells when they are activated through diverse processes, including post-transcriptional regulation by microRNAs (miRNAs). To identify the miRNAs that regulate CAF activation, we used NanoString to profile miRNA expression within normal mouse lung fibroblasts (LFs) and CAFs. Based on NanoString profiling, miR-196a was selected as a candidate that was up-regulated in CAFs. miR-196a-overexpressed LFs (LF-196a) promoted the migration and invasion of lung cancer cells in co-culture systems (Transwell migration and spheroid invasion assays). ANXA1 was confirmed as a direct target of miR-196a, and adding back ANXA1 to LF-196a restored the cancer cell invasion promoted by miR-196a. miR-196a increased CCL2 secretion in fibroblasts, and that was suppressed by ANXA1. Furthermore, blocking CCL2 impeded cancer spheroid invasion. In lung adenocarcinoma patients, high miR-196a expression was associated with poor prognosis. Collectively, our results suggest that CAF-specific miR-196a promotes lung cancer progression in the tumor microenvironment via ANXA1 and CCL2 and that miR-196a will be a good therapeutic target or biomarker in lung adenocarcinoma.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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