Adult Mesenchymal Stem Cells (MSCs) have a well-established tumor-homing capacity, highlighting potential as tumor-targeted delivery vehicles. MSCs secrete extracellular vesicle (EV)-encapsulated microRNAs, which play a role in intercellular communication. The aim of this study was to characterize a potential tumor suppressor microRNA, miR-379, and engineer MSCs to secrete EVs enriched with miR-379 for in vivo therapy of breast cancer. miR-379 expression was significantly reduced in lymph node metastases compared to primary tumor tissue from the same patients. A significant reduction in the rate of tumor formation and growth in vivo was observed in T47D breast cancer cells stably expressing miR-379. In more aggressive HER2-amplified HCC-1954 cells, HCC-379 and HCC-NTC tumor growth rate in vivo was similar, but increased tumor necrosis was observed in HCC-379 tumors. In response to elevated miR-379, COX-2 mRNA and protein was also significantly reduced in vitro and in vivo. MSCs were successfully engineered to secrete EVs enriched with miR-379, with the majority found to be of the appropriate size and morphology of exosomal EVs. Administration of MSC-379 or MSC-NTC cells, or EVs derived from either cell population, resulted in no adverse effects in vivo. While MSC-379 cells did not impact tumor growth, systemic administration of cell-free EVs enriched with miR-379 was demonstrated to have a therapeutic effect. The data presented support miR-379 as a potent tumor suppressor in breast cancer, mediated in part through regulation of COX-2. Exploiting the tumor-homing capacity of MSCs while engineering the cells to secrete EVs enriched with miR-379 holds exciting potential as an innovative therapy for metastatic breast cancer.

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Employing mesenchymal stem cells to support tumor-targeted delivery of extracellular vesicle (EV)-encapsulated microRNA-379.

Bladder cancer is the second most common urological malignancy in the US and is the most frequently diagnosed urological malignancy in China. An increasing amount of evidence indicates that microRNAs perform extremely important functions in many biological processes related to the formation and progression of cancers, including bladder cancer. Previous studies have reported that microRNA‑379-5p (miR-379-5p) is involved in tumour initiation and development in human cancers. However, the expression pattern, biological functions and the underlying mechanisms of miR-379-5p in bladder cancer remain unknown. The present study demonstrated that the expression levels of miR‑379-5p in bladder cancer tissues and cell lines were lower than the levels in adjacent normal tissues and the human bladder epithelial immortalized SV-HUC-1 cell line. Restoration of the expression of miR-379-5p inhibited bladder cancer cell proliferation, migration and invasion. Mouse double minute 2 (MDM2) was identified as a direct target gene of miR-379-5p. Furthermore, similar to miR-379-5p overexpression in bladder cancer cells, inhibition of MDM2 exerted tumor-suppressive effects. Rescue experiments showed that upregulation of MDM2 reversed the inhibitory effects of miR-379-5p on bladder cancer cell proliferation, migration and invasion. MDM2 was highly expressed and inversely correlated with miR-379-5p expression in bladder cancer tissues. These findings suggest that the miR-379-5p/MDM2 pathway plays an important role in bladder cancer and could serve as a potential candidate for bladder cancer therapeutics.

/pdf/microrna-379-5p-plays-a-tumor-suppressive-role-in-human-2kt2xqenmf.pdf

MicroRNA-379-5p plays a tumor-suppressive role in human bladder cancer growth and metastasis by directly targeting MDM2

Cervical cancer is the fourth most common malignancy among females worldwide. MicroRNA-379 (miR-379) is aberrantly expressed in multiple human cancer types. However, the expression pattern, roles, and detailed regulatory mechanisms of miR-379 in cervical cancer remain unknown. In this study, we found that miR-379 expression was downregulated in cervical cancer tissues and cell lines. Low miR-379 expression was correlated with International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and distant metastasis. Additionally, miR-379 overexpression suppressed the proliferation and invasion of cervical cancer cells. Furthermore, V-crk avian sarcoma virus CT10 oncogene homolog-like (CRKL) was identified as a direct target of miR-379 in cervical cancer. CRKL was upregulated in cancer tissues and negatively correlated with miR-379 expression. Moreover, restored CRKL expression rescued the inhibitory effects of miR-379 overexpression on cell proliferation and invasion. In conclusion, miR-379 may serve as a tumor suppressor in cervical cancer by directly targeting CRKL. Restoring miR-379 expression may be an effective strategy for the treatment of cervical cancer.

MicroRNA-379 Suppresses Cervical Cancer Cell Proliferation and Invasion by Directly Targeting V-crk Avian Sarcoma Virus CT10 Oncogene Homolog-Like (CRKL)

Progress in the application of exosomes as therapeutic vectors in tumor-targeted therapy.

AKR1C3 decreased CML sensitivity to Imatinib in bone marrow microenvironment via dysregulation of miR-379-5p

Objective
To investigate the effects of microRNA-379-5p (miR-379-5p) on proliferation, migration and invasion of hepatocellular carcinoma (HCC) cells.


Methods
Human HCC cell line HepG2 was infected with lentivirus carrying miR-379-5p (miR-379-5p group) or lentivirus carrying negative control sequences (negative control group). The untreated HepG2 cells represented blank control group. Cell proliferation was determined by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazoliumbromide (MTT) assays. Cell migration and invasion were assessed by Transwell assays. The mRNA and protein expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9 were analyzed by real-time quantitative polymerase chain reaction and Western blot, respectively.


Results
Compared with negative control group and blank control group, cell migration and invasion was significantly inhibited in miR-379-5p group (P 0.05). Furthermore, the mRNA and protein levels of MMP-2 and MMP-9 in miR-379-5p group were significantly lower than that in negative control group and blank control group (P<0.05).


Conclusion
miR-379-5p can suppress migration and invasion of HCC cell lines, which may be achieved by inhibiting MMP-2 and MMP-9 expressions.


Key words: 
Carcinoma, hepatoeellular; microRNA-379-5p; Migration; Invasion; Matrix metalloproteinase

Dong Sh

Papers

Effects of microRNA-379-5p on proliferation, migration and invasion of hepatocellular carcinoma cell line