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Background/Aims: An increasing body of evidence shows that long noncoding RNAs (lncRNAs) are involved in many different cancers. In this study, we aimed to investigate the competing endogenous RNA (ceRNA)-dependent mechanism by which the lncRNA GAS5 contributes to the development of breast cancer. Methods: A total of 68 breast cancer patients were enrolled, and breast cancer and adjacent normal tissues were collected. The human breast cancer cell lines MDA-MB-231, MDA-MB-453, BT549, SK-BR-3 and MCF-7 and human breast cell line MCF10A were utilized in this study. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting were performed to detect expression of relative factors. RNA immunoprecipitation (RIP) was used to evaluate the relationship between GAS5 and miR-23a, and a dual luciferase reporter gene assay was employed to assess the relationship between ATG3 and miR-23a. A subcutaneous xenograft nude mouse model was generated to examine the role of GAS5 and its regulatory pathway in autophagy. Results: GAS5 levels were frequently decreased in breast cancer tissues and cell lines, and its relatively low expression was closely related to a larger tumour size, advanced tumour-node-metastasis (TNM) stage and estrogen receptor-negative (ER-) breast cancer tissues. More importantly, we found that GAS5 promoted autophagy, with enhanced autophagosome formation after GAS5 overexpression. GAS5 was found to act as a microRNA sponge in a pathway that included miR-23a and its target gene ATG3. The GAS5-miR-23a-ATG3 axis significantly regulated autophagy in vivo and in vitro. Conclusions: In summary, we report that the GAS5-miR-23a-ATG3 axis can be regarded as a key regulator of autophagy pathways in breast cancer; it may constitute a promising biomarker and therapeutic target in the future.

Although the incidence of pancreatitis was higher, the overall stone clearance rate and risk of bleeding was lower with EPBD compared to EST.

Objective Exosomes derived from cancer-associated fibroblasts (CAFs) are known as important drivers of tumor progression. Previously, microRNA (miR)-148b-3p has been found to be upregulated in bladder cancers as well as in body fluids (blood, urine) of bladder cancer patients. Here, we aimed to explore the role of CAF-derived exosome miR-148b-3p in bladder cancer progression and chemosensitivity. Methods Transwell, MTT, flow cytometry and colony formation assays were applied to assess the effects of CAF-derived exosomes on bladder cancer cell metastasis, epithelial-mesenchymal transition (EMT) and chemosensitivity. A dual luciferase reporter assay was employed to evaluate the targeting relationship between miR-148b-3p and PTEN. Gain- and loss- of function assays were conducted to explore the roles of miR-148b-3p and PTEN in the behavior of bladder cancer cells. The role of PTEN in the metastasis, EMT and chemosensitivity of bladder cancer cells was assessed both in vivo and in vitro. Results We found that CAF-derived exosomes promoted the metastasis, EMT and drug resistance of bladder cancer cells. We also found that CAF-derived exosomes could directly transport miR-148b-3p into bladder cancer cells. In a xenograft mouse model we found that CAF-derived exosomes increased miR-148b-3p expression levels and promoted tumor proliferation, metastasis and drug resistance. PTEN was validated as a target of miR-148b-3p. Concordantly, we found that PTEN overexpression inhibited EMT, metastasis and chemoresistance in bladder cancer cells, reversing the tumor promoting effects of miR-148b-3p via the Wnt/β-catenin pathway. Conclusions Our results suggest that miR-148b-3p downregulation in CAF-derived exosomes, thereby inhibiting the Wnt/β-catenin pathway and promoting PTEN expression, may offer potential opportunities for bladder cancer treatment.

Therapeutic failure in prostate cancer (PC) is believed to result from its unusually invasive and metastatic nature. Cancer-associated fibroblasts (CAFs) are essential in the tumor microenvironment. We intended to study the role of CAF-derived exosomes in the context of PC and the potential regulatory mechanism associated with miR-423-5p and GREM2. CAF-derived exosomes decreased the chemosensitivity of parental PC cells and enhanced the drug resistance of drug-resistant cells. PC-associated fibroblast-derived exosomes carrying miR-423-5p increased the resistance of PC to taxane by inhibiting GREM2 through the TGF-β pathway. Inhibition of the TGF-β pathway partially reversed the increased drug resistance in PC cells induced by CAF-derived exosomes. Inhibition of miR-423-5p enhanced the drug sensitivity of PC cells in vivo. We showed that CAF-secreted exosomal miR-423-5p promoted chemotherapy resistance in PC by targeting GREM2 through the TGF-β pathway. This study may allow the development of novel approaches for PC.

This study aims to explore the mechanism of Circular RNA CDR1as implicating in regulating 5‐fluorouracil (5‐FU) chemosensitivity in breast cancer (BC) by competitively inhibiting miR‐7 to regulate CCNE1. Expressions of CDR1as and miR‐7 in 5‐FU‐resistant BC cells were determined by RT‐PCR. CCK‐8, colony formation assay and flow cytometry were applied to measure half maximal inhibitory concentration (IC50), 5‐Fu chemosensitivity and cell apoptosis. Western blot was used to detect the expressions of apoptosis‐related factors. CDR1as was elevated while miR‐7 was inhibited in 5‐FU‐resistant BC cells. Cells transfected with si‐CDR1as or miR‐7 mimic had decreased IC50 and colony formation rate, increased expressions of Bax/Bcl2 and cleaved‐Caspase‐3/Caspase‐3, indicating inhibition of CDR1as and overexpression of miR‐7 enhances the chemosensitity of 5‐FU‐resistant BC cells. Targetscan software indicates a binding site of CDR1as and miR‐7 and that CCNE1 is a target gene of miR‐7. miR‐7 can gather CDR1as in BC cells and can inhibit CCNE1. In comparison to si‐CDR1as group, CCNE1 was increased and chemosensitivity to 5‐Fu was suppressed in si‐CDR1as + miR‐7 inhibitor group. When compared with miR‐7 mimic group, CDR1as + miR‐7 mimic group had increased CCNE1 and decreased chemosensitivity to 5‐Fu. Nude mouse model of BC demonstrated that the growth of xenotransplanted tumour in si‐CDR1as + miR‐7 inhibitor group was faster than that in si‐CDR1as group. The tumour growth in CDR1as + miR‐7 mimic group was faster than that in miR‐7 mimic group. CDR1as may regulate chemosensitivity of 5‐FU‐resistant BC cells by inhibiting miR‐7 to regulate CCNE1.

In our study, we aimed to investigate the role of CDR1as during competitive inhibition of miR‐7 in the regulation of cisplatin chemosensitivity in breast cancer via regulating REGγ. RT‐qPCR was applied to detect the expression of CDR1as and miR‐7 in breast cancer tissues, breast cancer cell lines and corresponding drug‐resistant cell lines. The correlation between CDR1as and miR‐7 and between miR‐7 and REGγ was evaluated. MCF‐7‐R and MDA‐MB‐231‐R cells were selected followed by transfection of a series of mimics, inhibitors or siRNA. The effect of CDR1as on the half maximal inhibitor concentration (IC50), cisplatin sensitivity and cell apoptosis was also analysed. Furthermore, a subcutaneous xenograft nude mouse model was established to further confirm the effect of CDR1as on the chemosensitivity of breast cancer to cisplatin in vivo. Immunohistochemical staining was conducted to test the Ki‐67 expression in nude mice. A positive correlation was found between the drug resistance and CDR1as expression in breast cancer. CDR1as could increase the resistance of breast cancer cells to cisplatin. miR‐7 expression was low, while REGγ was highly expressed in MCF‐7‐R and MDA‐MB‐231‐R cells. CDR1as competitively inhibited miR‐7 and up‐regulated REGγ. Overexpression of miR‐7 could reverse the enhanced sensitivity of silenced CDR1as to drug‐resistant breast cancer cells. Additionally, in vivo experiments demonstrated that CDR1as mediated breast cancer occurrence and its sensitivity to cisplatin. Silencing CDR1as decreased Ki‐67 expression. Silencing CDR1as may inhibit the expression of REGγ by removing the competitive inhibitory effect on miR‐7 and thus enhancing the sensitivity of drug‐resistant breast cancer cells.

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