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Background: Nano‐sized extracellular vesicles secreted by cells play key roles in intercellular crosstalk, and appear to be an excellent biocompatible material as therapeutic cargoes in vivo. Previously, we have demonstrated that miR‐204‐5p is a key tumor suppressor that could inhibit tumor growth, metastasis and chemoresistance. Methods: A HEK293T cell line stably expressing miR‐204‐5p (293T‐miR‐204) was constructed by lentivirus transduction. Fluorescence real‐time quantitative PCR (qPCR) was applied to measure the expression of miR‐204‐5p. CCK‐8 and colony formation assays were used to evaluate the in vitro anticancer effects, and the flow cytometry was used to detect apoptosis. The in vivo therapeutic effects of exosomal miR‐204‐5p were evaluated using a xenograft mouse model. Western blots were used to detect the protein levels of CD63, Flotillin‐2, RAB22A and Bcl2. The protein levels of RAB22A and Bcl2 in tumor tissues were measured by immunohistochemistry staining. Results: MiR‐204‐5p was clearly upregulated in CRC cells after coculturing with 293T‐miR‐204 cell‐derived conditioned medium (CM) or exosomes. CCK‐8 and colony formation assays showed that the cell proliferation ability of CRC cells was clearly inhibited by 293T‐miR‐204 cell‐derived CM or exosomes. The inhibitory effects of exosomal miR‐204‐5p on cell proliferation were further confirmed in other types of cancers. Exosomal miR‐204‐5p could induce apoptosis and increase the sensitivity of cancer cells to the chemotherapeutic drug—5‐fluorourcil. In addition, exosomal miR‐204‐5p inhibited the tumor growth in mice. Western blot assay and IHC staining showed that the protein levels of miR‐204‐5p targets were clearly decreased in cancer cells or xenograft tissues treated with exosomal miR‐204‐5p. Conclusions: In this study, we confirmed that exosomal miR‐204‐5p could efficiently inhibit cancer cell proliferation, induce apoptosis and increase chemosensitivity by specifically suppressing the target genes of miR‐204‐5p in human cancer cells. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) play an important role in tumor progression. Small nucleolar RNA host gene 15 (SNHG15) is a lncRNA that has been confirmed to play an oncogenic role in multiple cancer types. However, its role in glycolysis and chemoresistance in colorectal cancer (CRC) is unclear. The expression of SNHG15 in CRC was analyzed using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases by bioinformatics methods. Cell Counting Kit-8 (CCK-8) and colony formation assays were used to evaluate cell viability. Cell sensitivity to 5-fluorouracil (5-FU) was detected by CCK-8. Glucose absorption and lactate production were used to evaluate the impact of SNHG15 on glycolysis. RNA-seq, real-time fluorescence quantitative reverse transcription PCR (RT–qPCR) and Western blotting (WB) were used to reveal the potential molecular mechanism of SNHG15 in CRC. SNHG15 was upregulated in CRC tissues compared with paired noncancerous tissues. Ectopic SNHG15 expression increased proliferation, 5-FU chemoresistance, and glycolysis in CRC cells. In contrast, SNHG15 knockdown inhibited CRC proliferation, 5-FU chemoresistance and glycolysis. Multiple pathways, including apoptosis and glycolysis, were potentially regulated by SNHG15 based on RNA-seq and pathway enrichment analyses. RT–qPCR and WB experiments confirmed that SNHG15 promoted the expression of TYMS, BCL2, GLUT1 and PKM2 in CRC cells. In conclusion, SNHG15 promotes 5-FU chemoresistance and glycolysis in CRC by potentially regulating the expression of TYMS, BCL2, GLUT1 and PKM2 and appears to be a new target for cancer therapy. [ABSTRACT FROM AUTHOR]

Signaling receptor and transporter of retinol STRA6 (STRA6) plays a primary role in transporting retinol. Several studies have reported that STRA6 is involved in several pathways related to tumorigenesis and progression. However, the exact functions and mechanisms of STRA6 in colorectal cancer (CRC) remain unclear. In our work, STRA6 was highly up-regulated in CRC and promoted the proliferation of CRC cells. Additionally, we discovered that STRA6 suppresses apoptosis partly by controlling BCL2 expression, which in turn causes CRC to become resistant to LOHP treatment. Our study demonstrates that STRA6 is a potential prognostic factor and oncogene in CRC by promoting CRC growth and chemoresistance. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR), a phenomenon that often occurs with drug treatment and is characterized by relapse or attenuation of drug efficacy, is almost unavoidable in colorectal cancer (CRC) patients receiving 5-fluorouracil (5-FU)-based chemotherapy. MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate gene expression. Our previous study has identified miR-139-5p as a potential tumor suppressor in CRC, but its role in chemoresistance of CRC has not been elucidated. In this study, we demonstrated that miR-139-5p was down-regulated either in CRC tumors receiving chemotherapy or in 5-FU-resistant CRC cell lines (HCT-8/5-FU and HCT-116/5-FU). Ectopic expression of miR-139-5p sensitized CRC cells to 5-FU by increasing 5-FU-induced apoptosis. In addition, miR-139-5p inhibited the expression of the miR-139-5p target gene NOTCH-1 and its downstream molecules MRP-1 and BCL-2, two key MDR-associated genes. Furthermore, silencing NOTCH-1 expression promoted the chemotherapeutic effects of 5-FU, and up-regulation of NOTCH-1 abrogated miR-139-5p-mediated sensitization to 5-FU in LoVo and HCT-116 cells. Taken together, our data indicate a new role of miR-139-5p/NOTCH-1 pathway in the drug resistance of CRC cells to 5-FU, which may be a promising therapeutic target for the anti-MDR treatment of CRC. [ABSTRACT FROM AUTHOR]