Suppressive function of bone marrow-derived mesenchymal stem cell-derived exosomal microRNA-187 in prostate cancer.

Application of bone marrow-derived mesenchymal stem cell-derived exosomes (BMSC-exos) in cancer treatment has been widely studied. Here, we elaborated the function of BMSC-exos containing microRNA-187 (miR-187) in prostate cancer. Differentially expressed miRs and genes were screened with microarray analysis. The relationship between CD276 and miR-187 in prostate cancer was evaluated. Following miR-187 mimic/inhibitor or CD276 overexpression transfection, their actions in prostate cancer cell biological processes were analyzed. Prostate cancer cells were then exposed to BMSC-exos that were treated with either miR-187 mimic/inhibitor or CD276 overexpression for pinpointing the in vitro and in vivo effects of exosomal miR-187. miR-187 was poorly expressed while CD276 was significantly upregulated in prostate cancer. Additionally, restoring miR-187 inhibited the prostate cancer cell malignant properties by targeting CD276. Upregulation of miR-187 led to declines in CD276 expression and the JAK3-STAT3-Slug signaling pathway. Next, BMSC-exos carrying miR-187 contributed to repressed cell malignant features as well as limited tumorigenicity and tumor metastasis. Collectively, this study demonstrated that BMSC-derived exosomal miR-187 restrained prostate cancer by reducing CD276/JAK3-STAT3-Slug axis.

miR-187-3p increases gemcitabine sensitivity in breast cancer cells by targeting FGF9 expression.

Breast cancer is the most common type of malignancy in women, which remains a significant health concern worldwide. Gemcitabine is a frequently applied anticancer pharmacological agent. However, the efficacy of gemcitabine is limited by chemoresistance. In the present study, a combination of reverse transcription quantitative-PCR, cell viability, flow cytometry, luciferase reporter assay and western blot analysis were performed to elucidate the potential effects of miR-187-3p on gemcitabine sensitivity in the breast cancer cell line, MDA-MB-231. The results revealed that miR-187-3p was significantly decreased in the breast cancer tumor tissues. Moreover, the overexpression of miR-187-3p significantly inhibited cell viability and promoted apoptosis in MDA-MB-231 cells. In addition, miR-187-3p overexpression enhanced the anti-proliferative and pro-apoptotic effects of gemcitabine, indicating that miR-187-3p regulated gemcitabine sensitivity in breast cancer cells. Mechanistically, miR-187-3p negatively regulated the expression of fibroblast growth factor 9 (FGF9) by binding to its 3'-untranslated region. Overexpression of FGF9 reversed the aforementioned effects of miR-187-3p overexpression on cell viability and apoptosis in the presence of gemcitabine. In conclusion, the present study indicated that miR-187-3p increased gemcitabine sensitivity in breast cancer cells by targeting FGF9 expression.

Downregulated miR-187 contributes to the keratinocytes hyperproliferation in psoriasis.

Psoriasis is a common chronic skin disease characterized by epidermal hyperplasia and inflammation. However, the pathogenesis of psoriasis is multifactorial and is not fully understood. MicroRNAs (miRNAs) represent a promising class of small, noncoding RNA molecules that have a large impact on cellular functions by regulating gene expression. Here we reported that microRNA-187 (miR-187), which is one of the most dynamic microRNAs identified in the deep screening miRNAs profile, is downregulated in inflammatory cytokines-stimulated keratinocytes and psoriatic skins. By luciferase activity assay and gain-of-function studies, we showed that miR-187 inhibits keratinocytes hyperproliferation by targeting CD276. Moreover, overexpression of miR-187 decreases acanthosis and reduces the disease severity in psoriasis mouse models. Taken together, the results of our study implies miR-187 as a critical factor in psoriasis pathogenesis, which could be a potent target for psoriasis treatment.

MiR-187 overexpression inhibits cervical cancer progression by targeting HPV16 E6.

Aberrantly expressed microRNAs contribute to the initiation and progression of human cancer. MiRNA-187 has been reported in nasopharyngeal, renal, pancreatic, prostate, and esophageal cancer, and acts as a tumor suppressor or oncogene. However, the underlying function of miRNA-187 in cervical cancer remains largely unexplored. In the present study, we demonstrated significantly miRNA-187 down-regulation in cervical cancer tissues and cell lines compared to their normal counterparts. Kaplan-Meier analysis revealed that decreased miRNA-187 was closely associated with shorter overall survival and relapse-free survival. Gain- and loss-of-function studies showed that miRNA-187 suppressed cervical cancer cell proliferation, migration, and invasion, and promoted cervical cancer cell apoptosis. Furthermore, luciferase reporter assay determined that human papillomavirus 16 E6 was a direct functional target of miRNA-187. Taken together, our findings indicate the essential role of miRNA-187 in suppressing cervical cancer progression and indicate a novel link between miRNA-187 and human papillomavirus 16 E6 in cervical cancer.

MicroRNA-187 inhibits tumor growth and invasion by directly targeting CD276 in colorectal cancer.

Aberrantly expressed microRNAs contribute to the initiation and progression of human cancers. However, the underlying functions of microRNA-187 (miR-187) in colorectal cancer (CRC) remain largely unexplored. Here, we demonstrated that miR-187 was significantly down-regulated in CRC tissues and cell lines compared to their normal counterparts. By Kaplan-Meier analysis, we revealed that decreased miR-187 expression was closely associated with shorter overall survival and relapse-free survival of patients with CRC. By gain- and loss-of-function studies, we showed that miR-187 remarkably suppressed CRC cell proliferation, migration, invasion, and promoted cell apoptosis. Furthermore, bioinformatics analysis and luciferase reporter assay identified that CD276 was the direct functional target of miR-187 in CRC. Genetic silencing of CD276 recapitulated similar phenotype as observed in over-expression of miR-187, and restoration of CD276 completely rescued the inhibitory effect of miR-187 in CRC cells. Taken together, our study implied the essential roles of miR-187 in suppressing CRC progression, and a novel link between miR-187 and CD276 in CRC.

MicroRNA-187, a downstream effector of TGFß pathway, suppresses Smad-mediated epithelial-mesenchymal transition in colorectal cancer.

Constitutive overactivation of TGFß signaling is a common event in human cancer progression and acts as a major inducer of epithelial-mesenchymal transition (EMT). In pre-metastatic colorectal cancer (CRC) cells, however, this cascade is tightly controlled and the underlying mechanism in TGFß stimulated hyperactivation of downstream Smad pathway remains elusive. In this study, expression of miR-187 was downregulated in colorectal cancer (CRC) compared with adjacent normal tissues. miR-187 could suppress the formation of aggressive phenotype in CRC and inactivate Smad pathway, thus preventing EMT. TGFß stimulation significantly suppressed the expression of miR-187, and overexpressed miR-187 counteracted the influence of TGFß on cell phenotype and downstream pathway. Furthermore, we found that miR-187 directly suppressed the expression of SOX4, NT5E and PTK6, which were identified as essential upstream effectors of Smad pathway. Together with the fact that high SOX4 or NT5E levels were associated with poor prognosis, we also demonstrated that downregulation of miR-187 was closely related to tumor metastasis and poor prognosis in CRC. These findings revealed a plausible mechanism for sustained TGFß activation in cancer progression and might have suggested a novel miR-187-based clinical intervention target for patients with advanced CRC.

Correlation Between IL-10 and microRNA-187 Expression in Epileptic Rat Hippocampus and Patients with Temporal Lobe Epilepsy.

Accumulating evidence is emerging that microRNAs (miRNAs) are key regulators in controlling neuroinflammatory responses that are known to play a potential role in the pathogenesis of temporal lobe epilepsy (TLE). The aim of the present study was to investigate the dynamic expression pattern of interleukin (IL)-10 as an anti-inflammatory cytokine and miR-187 as a post-transcriptional inflammation-related miRNA in the hippocampus of a rat model of status epilepticus (SE) and patients with TLE. We performed a real-time quantitative PCR and western blot on rat hippocampus 2 h, 7 days, 21 days and 60 days following pilocarpine-induced SE, and on hippocampus obtained from TLE patients and normal controls. To detect the relationship between IL-10 and miR-187 on neurons, lipopolysaccharide (LPS) and IL-10-stimulated neurons were performed. Furthermore, we identified the effect of antagonizing miR-187 by its antagomir on IL-10 secretion. Here, we reported that IL-10 secretion and miR-187 expression levels are inversely correlated after SE. In patients with TLE, the expression of IL-10 was also significantly upregulated, whereas miR-187 expression was significantly downregulated. Moreover, miR-187 expression was significantly reduced following IL-10 stimulation in an IL-10-dependent manner. On the other hand, antagonizing miR-187 promoted the production of IL-10 in hippocampal tissues of rat model of SE. Our findings demonstrate a critical role of miR-187 in the physiological regulation of IL-10 anti-inflammatory responses and elucidate the role of neuroinflammation in the pathogenesis of TLE. Therefore, modulation of the IL-10 / miR-187 axis may be a new therapeutic approach for TLE.

Down-regulation of microRNA-187*expression in colorectal cancer and its roles in promoting cell ;apoptosis / 中国癌症杂志

Background and purpose: MicroRNAs (miRNAs) play an important role in tumor biological behavior. miRNAs are down-regulated or up-regulated in various cancer types, triggering abnormal cell differentiation, proliferation and apoptosis. This study was designed to investigate the expression and clinical signiifcance of miR-187*in colorectal cancer (CRC), and further to investigate its roles in promoting cell apoptosis. Methods:The expressions of miR-187* in 40 CRC cases were examined by real-time quantitative reverse transcription-PCR (qRT-PCR). The relationship between miR-187*expression and clinical features of CRC was analyzed. HCT116 cells were transfected with a miR-187*mimic and the apoptosis of the transfected cells were examined by lfow cytometry (FCM). Results:The expression of miR-187*was down-regulated in CRC tissues 0.165 (0.106, 0.428) compared with those in normal tissues 0.334 (0.211, 0.712) (P<0.05), especially in mucinous carcinoma and older age CRC (P<0.05). Transfection of HCT116 cells with a miR-187*mimic up-regulated the expression of miR-187*and increased cell early apoptosis (P<0.05). Conclusion: The expression level of miR-187* was lower in CRC. miR-187* expression correlates with histological type and age. Transfection of HCT116 cells with a miR-187*mimic accelerates apoptosis of tumor cells, suggesting that miR-187*is a potent tumor suppressor.