Exosomal Circ-XIAP Promotes Docetaxel Resistance in Prostate Cancer by Regulating miR-1182/TPD52 Axis.

Exosomal circular RNAs (circRNAs) are involved in the pathogenesis of prostate cancer (PCa) and chemotherapy resistance. This research aimed to explore the function and molecular mechanism of circRNA X-linked inhibitor of apoptosis (circ-XIAP) in docetaxel (DTX) resistance of PCa. The expression of circ-XIAP, microRNA-1182 (miR-1182), tumor protein D52 (TPD52) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Exosomes were detected with transmission electron microscopy (TEM). Cluster of differentiation 63 (CD63), cluster of differentiation 9 (CD9) and TPD52 protein levels were detected by Western blot (WB). FIfty percent inhibitory concentration (IC50) of DTX and cell viability were determined using Cell Counting Kit-8 (CCK-8) assay. Colony formation assay was applied to assess colony-forming ability. Cell cycle distribution and apoptosis were analyzed by flow cytometry. Transwell assay was used for measuring cell migration and invasion. Dual-reporter luciferase assay was performed to confirm the interaction between miR-1182 and circ-XIAP or TPD52. The role of circ-XIAP in vivo was confirmed via the mice xenograft model. Circ-XIAP and TPD52 were upregulated and miR-1182 was downregulated in DTX-resistant PCa tissue specimens and cell lines. Circ-XIAP was also overexpressed in exosomes from DTX-resistant cells and could be transmitted via exosomes. Circ-XIAP knockdown enhanced DTX sensitivity by suppressing DTX-resistant cell proliferation, migration and invasion and inducing cell cycle arrest and apoptosis. Circ-XIAP directly targeted miR-1182, and the effects of circ-XIAP knockdown were reversed by downregulating miR-1182 in DTX-resistant cells. TPD52 was the target of miR-1182, and its upregulation weakened the promotive effect of miR-1182 on DTX sensitivity. Importantly, circ-XIAP depletion inhibited tumor growth and increased DTX sensitivity in vivo. Exosomal circ-XIAP promoted DTX resistance of PCa by regulating miR-1182/TPD52 axis, providing a promising therapeutic target for PCa chemotherapy.

Zhang H ，Li M ，Zhang J ，Shen Y ，Gui Q ... -  《Drug Design Development and Therapy》

Exosomal circRNA Scm-like with four malignant brain tumor domains 2 (circ-SFMBT2) enhances the docetaxel resistance of prostate cancer via the microRNA-136-5p/tribbles homolog 1 pathway.

Exosomal circular RNA was found to mediate cancer chemoresistance. However, whether exosomal circRNA Scm-like with four malignant brain tumor domains 2 (circ-SFMBT2) was involved in the chemoresistance of prostate cancer (PCa) remains unclear. The docetaxel (DTX) resistance of PCa cells was analyzed by Cell Counting Kit 8 assay. Quantitative real-time PCR was used to measure circSFMBT2, microRNA (miR)-136-5p and tribbles homolog 1 (TRIB1) expression. Cell proliferation, apoptosis, migration and invasion were analyzed by 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, wound-healing assay and transwell assay. RNA interaction was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Protein expression was measured by western blot analysis. Exosomes-extracted from cells were identified by transmission electron microscope, nanoparticles tracking analysis and western blot. Xenograft mice models were constructed to analyze the effect of exosomal circSFMBT2 on the DTX sensitivity of PCa tumors in vivo. CircSFMBT2 was upregulated in DTX-resistant PCa cells, and its knockdown enhanced the DTX sensitivity of DTX-resistant PCa cells by suppressing cell proliferation, migration, invasion and enhancing apoptosis. CircSFMBT2 severed as miR-136-5p sponge to positively regulate TRIB1. The regulation of circSFMBT2 knockdown on the DTX sensitivity of DTX-resistant PCa cells could be reversed by miR-136-5p inhibitor or TRIB1 overexpression. Exosomal circSFMBT2 from DTX-resistant PCa could increase the DTX resistance of normal PCa cells. In addition, exosomal circSFMBT2 also enhanced the DTX resistance of PCa tumors in vivo, and it was highly expressed in the serum of DTX-resistance PCa patients. Exosomal circSFMBT2 enhanced the DTX resistance of PCa by miR-136-5p/TRIB1 axis, indicating that circSFMBT2 might be a potential target for the treatment of PCa chemoresistance.

Tan X ，Song X ，Fan B ，Li M ，Zhang A ，Pei L ... -  《-》

Exosomal circ_PIP5K1A regulates the progression of non-small cell lung cancer and cisplatin sensitivity by miR-101/ABCC1 axis.

Shao N ，Song L ，Sun X 《-》

Circ_0003998 Regulates the Progression and Docetaxel Sensitivity of DTX-Resistant Non-Small Cell Lung Cancer Cells by the miR-136-5p/CORO1C Axis.

Zhang W ，Song C ，Ren X 《-》

Exosomal circ_0007385 enhances non-small cell lung cancer cell proliferation and stemness via regulating miR-1253/FAM83A axis.

Exosomes are critical mediators of intercellular communication in the tumor microenvironment. Exosomal circular RNAs (circRNAs) can act as biomarkers and play crucial roles in many cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to explore the functions and regulatory mechanism of exosomal circ_0007385 in NSCLC. The expression levels of circ_0007385, microRNA-1253 (miR-1253), family with sequence similarity 83, member A (FAM83A) mRNA were determined by quantitative real-time PCR (qRT-PCR). Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (Edu), and colony formation assays were utilized to determine cell proliferation ability. Sphere formation efficiency was determined by sphere formation assay. All protein levels were detected by western blot assay. Exosomes were detected using transmission electron microscopy analysis. Size distribution of exosomes was analyzed by nanoparticle tracking analysis. The interaction between miR-1253 and circ_0007385 or FAM83A was confirmed by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. Mice xenograft model was established to verify the function of circ_0007385 in vivo. Circ_0007385 was upregulated in NSCLC tissues and cells. Knockdown of circ_0007385 inhibited NSCLC cell proliferation and stemness, while exosomal circ_0007385 facilitated NSCLC cell proliferation and stemness. In addition, miR-1253 was a direct target of circ_0007385, and miR-1253 reversed the inhibitory effects of circ_0007385 on cell proliferation and stemness in NSCLC cells. Moreover, FAM83A was a direct target of miR-1253, and miR-1253 suppressed NSCLC cell proliferation and stemness by targeting FAM83A. Furthermore, circ_0007385 knockdown inhibited tumor growth in vivo. Exosomal circ_0007385 promoted NSCLC cell proliferation and stemness by regulating miR-1253/FAM83A axis.

Ning Z ，Tian Y ，Li Y ，Zhao X ，Zhang J ，Wang C ，Hu J ，Shen H ，Wu W ... -  《-》