Tumor-Derived Exosomal Circular RNA Pinin Induces FGF13 Expression to Promote Colorectal Cancer Progression through miR-1225-5p
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Background/Aims: Colorectal cancer (CRC) is a common malignant tumor, and circular RNAs (circRNAs) are abnormally expressed in CRC. However, the function and underlying mechanism of circRNA pinin (circ-PNN; hsa_circ_0101802) in CRC remain unclear. Methods: Exosomes were isolated from the plasma of CRC patients and identified by transmission electron microscopy and Western blotting. The RNA expression levels of circ-PNN, miR-1225-5p, and fibroblast growth factor 13 (FGF13) were measured by quantitative real-time polymerase chain reaction. Cell proliferation was detected by Cell Counting K-8, colony formation, and 5-ethynyl-2’-deoxyuridine assays. Cell apoptosis was assessed by flow cytometry. The expression of apoptosis and metastasis-related proteins was evaluated by Western blotting. The associations among circ-PNN, miR-1225-5p, and FGF13 were confirmed by dual-luciferase report assay and RNA immunoprecipitation assay. A xenograft model was used to verify the function of circ-PNN in tumor formation in vivo. Results: circ-PNN expression was upregulated in plasmic exosomes derived from CRC patients. The expression of circ-PNN and FGF13 was upregulated, while miR-1225-5p expression was downregulated in CRC cells incubated with plasmic exosomes derived from CRC patients. Tumor-derived exosomes promoted the proliferation, migration, and invasion but inhibited apoptosis of CRC cells. Moreover, the addition of tumor-derived exosomes partly reversed the inhibitory effect of circ-PNN knockdown on CRC tumor progression in vitro and in vivo. Thus, circ-PNN acts as a sponge for miR-1225-5p to regulate FGF13 expression. Conclusions: Tumor-derived exosomal circ-PNN promoted CRC progression through the regulation of the miR-1225-5p/FGF13 pathway, providing a potential therapeutic target for CRC.
Abstract
Background/Aims: Colorectal cancer (CRC) is a common malignant tumor, and circular RNAs (circRNAs) are abnormally expressed in CRC. However, the function and underlying mechanism of circRNA pinin (circ-PNN; hsa_circ_0101802) in CRC remain unclear. Methods: Exosomes were isolated from the plasma of CRC patients and identified by transmission electron microscopy and Western blotting. The RNA expression levels of circ-PNN, miR-1225-5p, and fibroblast growth factor 13 (FGF13) were measured by quantitative real-time polymerase chain reaction. Cell proliferation was detected by Cell Counting K-8, colony formation, and 5-ethynyl-2’-deoxyuridine assays. Cell apoptosis was assessed by flow cytometry. The expression of apoptosis and metastasis-related proteins was evaluated by Western blotting. The associations among circ-PNN, miR-1225-5p, and FGF13 were confirmed by dual-luciferase report assay and RNA immunoprecipitation assay. A xenograft model was used to verify the function of circ-PNN in tumor formation in vivo. Results: circ-PNN expression was upregulated in plasmic exosomes derived from CRC patients. The expression of circ-PNN and FGF13 was upregulated, while miR-1225-5p expression was downregulated in CRC cells incubated with plasmic exosomes derived from CRC patients. Tumor-derived exosomes promoted the proliferation, migration, and invasion but inhibited apoptosis of CRC cells. Moreover, the addition of tumor-derived exosomes partly reversed the inhibitory effect of circ-PNN knockdown on CRC tumor progression in vitro and in vivo. Thus, circ-PNN acts as a sponge for miR-1225-5p to regulate FGF13 expression. Conclusions: Tumor-derived exosomal circ-PNN promoted CRC progression through the regulation of the miR-1225-5p/FGF13 pathway, providing a potential therapeutic target for CRC.
참고문헌 (43)
- Kuipers EJ, "Colorectal cancer", Nat Rev Dis Primers, 1, pp.15065~ (2015)
- Brody H, "Colorectal cancer", Nature, 521, pp.S1~ (2015)
- Goldstein DA, "Metastatic colorectal cancer : a systematic review of the value of current therapies", Clin Colorectal Cancer, 15, pp.1~6 (2016)
- Siegel RL, "Colorectal cancer statistics, 2020", CA Cancer J Clin, 70, pp.145~164 (2020)
- Sun Z, "Effect of exosomal miRNA on cancer biology and clinical applications", Mol Cancer, 17, pp.147~ (2018)
- Tan A, "Exosomes as nano-theranostic delivery platforms for gene therapy", Adv Drug Deliv Rev, 65, pp.357~367 (2013)
- Xie Y, "The role of exosomal noncoding RNAs in cancer", Mol Cancer, 18, pp.37~ (2019)
- Colombo M, "Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles", Annu Rev Cell Dev Biol, 30, pp.255~289 (2014)
- Wang Y, "Exosomal circRNAs : biogenesis, effect and application in human diseases", Mol Cancer, 18, pp.116~ (2019)
- Wang M, "Emerging function and clinical significance of exosomal circRNAs in cancer", Mol Ther Nucleic Acids, 21, pp.367~383 (2020)
- Pan B, "Identification of serum exosomal hsa-circ-0004771 as a novel diagnostic biomarker of colorectal cancer", Front Genet, 10, pp.1096~ (2019)
- Granados-Riveron JT, "The complexity of the translation ability of circRNAs", Biochim Biophys Acta, 1859, pp.1245~1251 (2016)
- Ren C, "Circular RNA hsa_circ_0001178 facilitates the invasion and metastasis of colorectal cancer through upregulating ZEB1 via sponging multiple miRNAs", Biol Chem, 401, pp.487~496 (2020)
- Zhang ZJ, "Circular RNA circDENND4C facilitates proliferation, migration and glycolysis of colorectal cancer cells through miR-760", GLUT1axis, 2020, pp.24, 2387~2400
- Xie Y, "RNA-seq profiling of serum exosomal circular RNAs reveals circ-PNN as a potential biomarker for human colorectal cancer", Front Oncol, 10, pp.982~ (2020)
- Zang J, "The interaction of circRNAs and RNA binding proteins : an important part of circRNA maintenance and function", J Neurosci Res, 98, pp.87~97 (2020)
- Cheng DL, "Competing endogenous RNA interplay in cancer : mechanism, methodology, and perspectives", Tumour Biol, 36, pp.479~488 (2015)
- Chen J, "Circular RNA circRHOBTB3represses metastasis by regulating the HuR-mediated mRNA stability of PTBP1 in colorectal cancer", Theranostics, 11, pp.7507~7526 (2021)
- Chen F, "Circular RNA ubiquitin-associated protein 2 enhances autophagy and promotes colorectal cancer progression and metastasis via miR-582-5p", FOXO1 signaling, 2021, pp.48, 1091~1103
- Yu L, "Increased expression of fibroblast growth factor 13 in prostate cancer is associated with shortened time to biochemical recurrence after radical prostatectomy", Int J Cancer, 139, pp.140~152 (2016)
- Lu H, "FGF13 interaction with SHCBP1activates AKT-GSK3α", β signaling and promotes the proliferation of A549 cells, 2020, pp.21, 1014~1024
- Song JJ, "MiR-10b suppresses the growth and metastasis of colorectal cancer cell by targeting FGF13", Eur Rev Med Pharmacol Sci, 23, pp.576~587 (2019)
- Johnstone CN, "FGF13 promotes metastasis of triple-negative breast cancer", Int J Cancer, 147, pp.230~243 (2020)
- Hollern DP, "E2F1 drives breast cancer metastasis by regulating the target gene FGF13and altering cell migration", Sci Rep, 9, pp.10718~ (2019)
- Wu Y, "lncRNA LINC00963downregulation regulates colorectal cancer tumorigenesis and progression via the miR‑10b", FGF13 axis, 2021, pp.23, 211~
- Valadi H, "Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells", Nat Cell Biol, 9, pp.654~659 (2007)
- Sun D, "Circ_0058124upregulates MAPK1 expression to promote proliferation, metastasis and metabolic abilities in thyroid cancer through sponging miR-940", Onco Targets Ther, 13, pp.1569~1581 (2020)
- Huang DW, "CD155 expression and its correlation with clinicopathologic characteristics, angiogenesis, and prognosis in human cholangiocarcinoma", Onco Targets Ther, 10, pp.3817~3825 (2017)
- Li C, "Circular RNAs : pivotal molecular regulators and novel diagnostic and prognostic biomarkers in non-small cell lung cancer", J Cancer Res Clin Oncol, 145, pp.2875~2889 (2019)
- Zhang X, "Hsa_circ_0026628 promotes the development of colorectal cancer by targeting SP1 to activate the Wnt", β-catenin pathway, 2021, pp.12, 802~
- Chen Z, "Identification of cis-HOX-HOXC10axis as a therapeutic target for colorectal tumor-initiating cells without APC mutations", Cell Rep, 36, pp.109431~ (2021)
- Zhang C, "Circular RNA hsa_circ_0006401 promotes proliferation and metastasis in colorectal carcinoma", Cell Death Dis, 12, pp.443~ (2021)
- Hansen TB, "Natural RNA circles function as efficient microRNA sponges", Nature, 495, pp.384~388 (2013)
- Xu S, "CircGNG4 promotes the progression of prostate cancer by sponging miR-223to enhance EYA3", c-myc expression, 2021, pp.9, 684125~
- Yang B, "Circular RNA circ_001422 promotes the progression and metastasis of osteosarcoma via the miR-195-5p", FGF2, Akt axis, pp.J Exp Clin Cancer Res, 2021[DOI]
- Liang M, "Circular RNA hsa_circ_0110389promotes gastric cancer progression through upregulating SORT1 via sponging miR-127-5p and miR-136-5p", Cell Death Dis, 12, pp.639~ (2021)
- Yang K, "Rosmarinic acid inhibits migration, invasion, and p38", AP-1 signaling via miR-1225-5p in colorectal cancer cells, 2021, pp.41, 284~293
- Simons M, "Exosomes : vesicular carriers for intercellular communication", Curr Opin Cell Biol, 21, pp.575~581 (2009)
- Sun Z, "Emerging role of exosome-derived long non-coding RNAs in tumor microenvironment", Mol Cancer, 17, pp.82~ (2018)
- Zhang J, "Exosome and exosomal microRNA : trafficking, sorting, and function", Genomics Proteomics Bioinformatics, 13, pp.17~24 (2015)
- Liu T, "Exosome-transmitted miR-128-3p increase chemosensitivity of oxaliplatin-resistant colorectal cancer", Mol Cancer, 18, pp.43~ (2019)
- Sun J, "Tumor exosome promotes Th17cell differentiation by transmitting the lncRNA CRNDE-h in colorectal cancer", Cell Death Dis, 12, pp.123~ (2021)
- Jiang Z, "Exosomal circEPB41L2serves as a sponge for miR-21-5p and miR-942-5p to suppress colorectal cancer progression by regulating the PTEN", AKT signalling pathway, 2021, pp.51, e13581~