microRNAs (miRNAs) have emerged as major regulators of the initiation and progression of human cancers, including breast cancer. The aim of this study is to determine the expression pattern of miR-96 in breast cancer and to investigate its biological role during tumorigenesis. We showed that miR-96 was significantly upregulated in breast cancer. We then investigated its function and found that miR-96 significantly promoted cell proliferation, migration and invasion in vitro and enhanced tumor growth in vivo. Furthermore, we explored the molecular mechanisms by which miR-96 contributes to breast cancer progression and identified PTPN9 (protein tyrosine phosphatase, non-receptor type 9) as a direct target gene of miR-96. Finally, we showed that PTPN9 had opposite effects to those of miR-96 on breast cancer cells, suggesting that miR-96 may promote breast tumorigenesis by silencing PTPN9. Taken together, this study highlights an important role for miR-96 in the regulation of PTPN9 in breast cancer cells and may provide insight into the molecular mechanisms of breast carcinogenesis.

RNAi therapy has undergone two stages of development, direct injection of synthetic siRNAs and delivery with artificial vehicles or conjugated ligands; both have not solved the problem of efficient in vivo siRNA delivery. Here, we present a proof-of-principle strategy that reprogrammes host liver with genetic circuits to direct the synthesis and self-assembly of siRNAs into secretory exosomes and facilitate the in vivo delivery of siRNAs through circulating exosomes. By combination of different genetic circuit modules, in vivo assembled siRNAs are systematically distributed to multiple tissues or targeted to specific tissues (e.g., brain), inducing potent target gene silencing in these tissues. The therapeutic value of our strategy is demonstrated by programmed silencing of critical targets associated with various diseases, including EGFR/KRAS in lung cancer, EGFR/TNC in glioblastoma and PTP1B in obesity. Overall, our strategy represents a next generation RNAi therapeutics, which makes RNAi therapy feasible.

Programmed cell death 4 (PDCD4) is a RNA-binding protein that acts as a tumor suppressor in many cancer types, including colorectal cancer (CRC). During CRC carcinogenesis, PDCD4 protein levels remarkably decrease, but the underlying molecular mechanism for decreased PDCD4 expression is not fully understood. In this study, we performed bioinformatics analysis to identify miRNAs that potentially target PDCD4. We demonstrated miR-181b as a direct regulator of PDCD4. We further showed that activation of IL6/STAT3 signaling pathway increased miR-181b expression and consequently resulted in downregulation of PDCD4 in CRC cells. In addition, we investigated the biological effects of PDCD4 inhibition by miR-181b both in vitro and in vivo and found that miR-181b could promote cell proliferation and migration and suppress apoptosis in CRC cells and accelerate tumor growth in xenograft mice, potentially through targeting PDCD4. Taken together, this study highlights an oncomiR role for miR-181b in regulating PDCD4 in CRC and suggests that miR-181b may be a novel molecular therapeutic target for CRC.Electronic supplementary materialThe online version of this article (doi:10.1007/s13238-016-0313-2) contains supplementary material, which is available to authorized users.

Nonreceptor tyrosine kinase c‐Src, also known as Src, is a potent oncogene involved in a series of biological processes including cell growth, differentiation, and apoptosis; however, its expression pattern and function in esophageal cancer is poorly addressed. In this study, abnormal overexpression of Src protein was observed in esophageal cancer tissues, which fuelled the speculation that microRNA‐mediated posttranscriptional regulatory mechanism might be involved. Bioinformatic analyses were applied to identify miRNAs that could potentially target Src. miR‐1 was predicted and further validated as a direct repressor of Src. Moreover, we manipulated knockdown and overexpression experiment on TE‐1 and TE‐10 cells to demonstrate miR‐1 suppressed proliferation and promoted apoptosis in esophageal cancer cells by inhibiting Src. Taken together, this study underlines a negative regulatory mechanism in which miR‐1 serves as a suppressor of Src in esophageal cancer cells and may provide insights into novel therapeutic approaches for esophageal cancer.

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Background and Objective: Gastric Carcinoma (GC) is categorized among malignant tumours with an extremely increased fatality rate, with an incidence constantly rising in recent years. Accumulating studies have pointed out that lncRNA may be the breakthrough in the fight against tumour diseases. The purpose of this investigation was to explore the mechanism of lncRNA PVT1 on gastric carcinoma cells. Materials and Methods: SGC7901 and MGC803 GC cell multiplication, invasion and apoptosis were studied under altering expressions of PVT1 and miR-423-5p. The interaction between both was further confirmed by the Dual-Luciferase Reporter Assay (DLRA). Results: Silencing PVT1 and increasing miR-423-5p hampered GC cell multiplication and invasiveness capacity and enhanced apoptosis while overexpression had opposite effects (p<0.05). The online target gene prediction website identified a reciprocal binding locus between PVT1 and miR-423-5p and DLRA confirmed the targeting relationship (p<0.05). After inhibiting PVT1, miR-423-5p in GC cells increased (p<0.05). Moreover, the salvage experiment demonstrated that reduced expression levels of PVT1 on GC cells were restored by simultaneously inhibiting miR-423-5p (p>0.05). Conclusion: PVT1 participates in gastric carcinogenesis and progression through the targeted inhibition of miR-423-5p to promote cell activity and reduce apoptosis, which may be a breakthrough in GC research regarding its diagnosis and treatment.

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