Loss of exosomal miR-148b from cancer-associated fibroblasts promotes endometrial cancer cell invasion and cancer metastasis.

Cancer-associated fibroblasts (CAFs) play crucial roles in tumor progression, given the dependence of cancer cells on stromal support. Therefore, understanding how CAFs communicate with endometrial cancer cell in tumor environment is important for endometrial cancer therapy. Exosomes, which contain proteins and noncoding RNA, are identified as an important mediator of cell-cell communication. However, the function of exosomes in endometrial cancer metastasis remains poorly understood. In the current study we found that CAF-derived exosomes significantly promoted endometrial cancer cell invasion comparing to those from normal fibroblasts (NFs). We identified a significant decrease of miR-148b in CAFs and CAFs-derived exosomes. By exogenously transfect microRNAs, we demonstrated that miR-148b could be transferred from CAFs to endometrial cancer cell through exosomes. In vitro and in vivo studies further revealed that miR-148b functioned as a tumor suppressor by directly binding to its downstream target gene, DNMT1 to suppress endometrial cancer metastasis. In endometrial cancer DNMT1 presented a potential role in enhancing cancer cell metastasis by inducing epithelial-mesenchymal transition (EMT). Therefore, downregulated miR-148b induced EMT of endometrial cancer cell as a result of relieving the suppression of DNMT1. Taken together, these results suggest that CAFs-mediated endometrial cancer progression is partially related to the loss of miR-148b in the exosomes of CAFs and promoting the transfer of stromal cell-derived miR-148b might be a potential treatment to prevent endometrial cancer progression.

Li BL ，Lu W ，Qu JJ ，Ye L ，Du GQ ，Wan XP ... -  《-》

Downregulated exosomal microRNA-148b-3p in cancer associated fibroblasts enhance chemosensitivity of bladder cancer cells by downregulating the Wnt/β-catenin pathway and upregulating PTEN.

Shan G ，Zhou X ，Gu J ，Zhou D ，Cheng W ，Wu H ，Wang Y ，Tang T ，Wang X ... -  《-》

Loss of exosomal miR-320a from cancer-associated fibroblasts contributes to HCC proliferation and metastasis.

Cancer-associated fibroblasts (CAFs) play a pivotal role in regulating tumour progression. Therefore, understanding how CAFs communicate with hepatocellular carcinoma (HCC) is crucial for HCC therapy. Recently, exosomes have been considered an important "messenger" between cells. In this study, we performed microRNA (miRNA) sequencing of exosomes derived from CAFs and corresponding para-cancer fibroblasts (PAFs) of HCC patients. We found a significant reduction in the miR-320a level in CAF-derived exosomes. Using exogenous miRNAs, we demonstrated that stromal cells could transfer miRNA to HCC cells. In vitro and in vivo studies further revealed that miR-320a could function as an antitumour miRNA by binding to its direct downstream target PBX3 to suppress HCC cell proliferation, migration and metastasis. The miR-320a-PBX3 pathway inhibited tumour progression by suppressing the activation of the MAPK pathway, which could induce the epithelial-mesenchymal transition and upregulate cyclin-dependent kinase 2 (CDK2) and MMP2 expression to promote cell proliferation and metastasis. In xenograft experiments involving CAFs mixed with MHCC97-H cells, miR-320a overexpression in CAFs could inhibit tumourigenesis. Therefore, these data suggest that CAF-mediated HCC tumour progression is partially related to the loss of antitumour miR-320a in the exosomes of CAFs and that promoting the transfer of stromal cell-derived miR-320a might be a potential treatment option to overcome HCC progression.

Zhang Z ，Li X ，Sun W ，Yue S ，Yang J ，Li J ，Ma B ，Wang J ，Yang X ，Pu M ，Ruan B ，Zhao G ，Huang Q ，Wang L ，Tao K ，Dou K ... -  《-》

CAFs secreted exosomes promote metastasis and chemotherapy resistance by enhancing cell stemness and epithelial-mesenchymal transition in colorectal cancer.

Hu JL ，Wang W ，Lan XL ，Zeng ZC ，Liang YS ，Yan YR ，Song FY ，Wang FF ，Zhu XH ，Liao WJ ，Liao WT ，Ding YQ ，Liang L ... -  《Molecular Cancer》

Loss of exosomal miR-146a-5p from cancer-associated fibroblasts after androgen deprivation therapy contributes to prostate cancer metastasis.

Zhang Y ，Zhao J ，Ding M ，Su Y ，Cui D ，Jiang C ，Zhao S ，Jia G ，Wang X ，Ruan Y ，Jing Y ，Xia S ，Han B ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》