TY - JOUR
T1 - Cancer-associated fibroblasts promote hepatocellular carcinoma progression through downregulation of exosomal miR-150-3p
AU - Yugawa, Kyohei
AU - Yoshizumi, Tomoharu
AU - Mano, Yohei
AU - Itoh, Shinji
AU - Harada, Noboru
AU - Ikegami, Toru
AU - Kohashi, Kenichi
AU - Oda, Yoshinao
AU - Mori, Masaki
N1 - Funding Information:
We would like to thank Ms. Saori Tsurumaru, Ms. Asuka Nakamura, Ms. Emi Kamiya, Ms. Yuko Kubota, and Ms. Miki Nakashima for their technical support. We also thank Marla Brunker, from Edanz Group ( www.edanzediting.com/ac ), for editing a draft of this manuscript. This study was supported by the following three grants: JSPS KAKENHI , a Grant-in-Aid from the Ministry of Health, Labour, and Welfare, Japan (number JP-16K10576 ), JSPS KAKEN Grant (number JP-19K18092 ) and the program for Basic and Clinical Research on Hepatitis from Japan Agency for Medical Research and Development, AMED . The funding sources had no role in the collection, analysis, or interpretation of the data, or in the decision to submit the article for publication.
Funding Information:
We would like to thank Ms. Saori Tsurumaru, Ms. Asuka Nakamura, Ms. Emi Kamiya, Ms. Yuko Kubota, and Ms. Miki Nakashima for their technical support. We also thank Marla Brunker, from Edanz Group (www.edanzediting.com/ac), for editing a draft of this manuscript. This study was supported by the following three grants: JSPS KAKENHI, a Grant-in-Aid from the Ministry of Health, Labour, and Welfare, Japan (number JP-16K10576), JSPS KAKEN Grant (number JP-19K18092) and the program for Basic and Clinical Research on Hepatitis from Japan Agency for Medical Research and Development, AMED. The funding sources had no role in the collection, analysis, or interpretation of the data, or in the decision to submit the article for publication.
Publisher Copyright:
© 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology
PY - 2020
Y1 - 2020
N2 - Purpose: Hepatocellular carcinoma (HCC) is a common and deadly cancer. The prognosis of HCC is poor and is related to tumor progression. The malignant potential of HCC is regulated by the tumor microenvironment (TME). As cancer-associated fibroblasts (CAFs) help regulate tumor progression, understanding how they function in HCC could improve patient outcomes. The aim of this study was to determine whether specific microRNAs (miRNAs) in exosomes derived from CAFs might be involved in HCC progression. Methods: MiRNA microarray assay was used to analyze miRNA profiles of exosomes derived from CAFs and normal fibroblasts (NFs) in HCC. Migration and invasion assays were performed to examine the effects of miR-150-3p on HCC in vitro. In addition, the relationships between prognosis of HCC patients and miR-150-3p expression in HCC tissues and plasma exosomes were retrospectively analyzed. Results: MiR-150-3p was significantly reduced in CAFs-derived exosomes, and inhibited HCC migration and invasiveness. MiR-150-3p was transferred from CAFs transfected miR-150-3p to HCC cells through exosomes, and abrogated HCC migration and invasiveness. Furthermore, low miR-150-3p expression in HCC tissues was a significant risk factor for recurrence in HCC patients. More importantly, survival rate in patients with low miR-150-3p levels in plasma exosomes was significantly poor compared with that in patients with high miR-150-3p levels. Conclusions: Overall, our findings suggest that the loss of antitumoral miR-150-3p in CAFs-derived exosomes greatly promotes HCC progression. Exosomal miR-150-3p is a potential prognostic biomarker, and transferring miR-150-3p-loaded exosomes to HCC cells might become a novel therapeutic option.
AB - Purpose: Hepatocellular carcinoma (HCC) is a common and deadly cancer. The prognosis of HCC is poor and is related to tumor progression. The malignant potential of HCC is regulated by the tumor microenvironment (TME). As cancer-associated fibroblasts (CAFs) help regulate tumor progression, understanding how they function in HCC could improve patient outcomes. The aim of this study was to determine whether specific microRNAs (miRNAs) in exosomes derived from CAFs might be involved in HCC progression. Methods: MiRNA microarray assay was used to analyze miRNA profiles of exosomes derived from CAFs and normal fibroblasts (NFs) in HCC. Migration and invasion assays were performed to examine the effects of miR-150-3p on HCC in vitro. In addition, the relationships between prognosis of HCC patients and miR-150-3p expression in HCC tissues and plasma exosomes were retrospectively analyzed. Results: MiR-150-3p was significantly reduced in CAFs-derived exosomes, and inhibited HCC migration and invasiveness. MiR-150-3p was transferred from CAFs transfected miR-150-3p to HCC cells through exosomes, and abrogated HCC migration and invasiveness. Furthermore, low miR-150-3p expression in HCC tissues was a significant risk factor for recurrence in HCC patients. More importantly, survival rate in patients with low miR-150-3p levels in plasma exosomes was significantly poor compared with that in patients with high miR-150-3p levels. Conclusions: Overall, our findings suggest that the loss of antitumoral miR-150-3p in CAFs-derived exosomes greatly promotes HCC progression. Exosomal miR-150-3p is a potential prognostic biomarker, and transferring miR-150-3p-loaded exosomes to HCC cells might become a novel therapeutic option.
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U2 - 10.1016/j.ejso.2020.08.002
DO - 10.1016/j.ejso.2020.08.002
M3 - Article
C2 - 32883551
AN - SCOPUS:85089982622
SN - 0748-7983
VL - 47
SP - 384
EP - 393
JO - European Journal of Surgical Oncology
JF - European Journal of Surgical Oncology
IS - 2
ER -
