CircCOL1A2 Sponges MiR-1286 to Promote Cell Invasion and Migration of Gastric Cancer by Elevating Expression of USP10 to Downregulate RFC2 Ubiquitination Level
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Gastric cancers (GC) are generally malignant tumors, occurring with high incidence and threatening public health around the world. Circular RNAs (circRNAs) play crucial roles in modulating various cancers, including GC. However, the functions of circRNAs and their regulatory mechanism in colorectal cancer (CRC) remain largely unknown. This study focuses on both the role of circCOL1A2 in CRC progression as well as its downstream molecular mechanism. Quantitative polymerase chain reaction (qPCR) and western blot were adopted for gene expression analysis. Functional experiments were performed to study the biological functions. Fluorescence in situ hybridization (FISH) and subcellular fraction assays were employed to detect the subcellular distribution. Luciferase reporter, RNA-binding protein immunoprecipitation (RIP), co-immunoprecipitation (Co- IP), RNA pull-down, and immunofluorescence (IF) and immunoprecipitation (IP) assays were used to explore the underlying mechanisms. Our results found circCOL1A2 to be not only upregulated in GC cells, but that it also propels the migration and invasion of GC cells. CircCOL1A2 functions as a competing endogenous RNA (ceRNA) by sequestering microRNA-1286 (miR-1286) to modulate ubiquitin-specific peptidase 10 (USP10), which in turn spurs the migration and invasion of GC cells by regulating RFC2. In sum, CircCOL1A2 sponges miR-1286 to promote cell invasion and migration of GC by elevating the expression of USP10 to downregulate the level of RFC2 ubiquitination. Our study offers a potential novel target for the early diagnosis and treatment of GC.
Abstract
Gastric cancers (GC) are generally malignant tumors, occurring with high incidence and threatening public health around the world. Circular RNAs (circRNAs) play crucial roles in modulating various cancers, including GC. However, the functions of circRNAs and their regulatory mechanism in colorectal cancer (CRC) remain largely unknown. This study focuses on both the role of circCOL1A2 in CRC progression as well as its downstream molecular mechanism. Quantitative polymerase chain reaction (qPCR) and western blot were adopted for gene expression analysis. Functional experiments were performed to study the biological functions. Fluorescence in situ hybridization (FISH) and subcellular fraction assays were employed to detect the subcellular distribution. Luciferase reporter, RNA-binding protein immunoprecipitation (RIP), co-immunoprecipitation (Co- IP), RNA pull-down, and immunofluorescence (IF) and immunoprecipitation (IP) assays were used to explore the underlying mechanisms. Our results found circCOL1A2 to be not only upregulated in GC cells, but that it also propels the migration and invasion of GC cells. CircCOL1A2 functions as a competing endogenous RNA (ceRNA) by sequestering microRNA-1286 (miR-1286) to modulate ubiquitin-specific peptidase 10 (USP10), which in turn spurs the migration and invasion of GC cells by regulating RFC2. In sum, CircCOL1A2 sponges miR-1286 to promote cell invasion and migration of GC by elevating the expression of USP10 to downregulate the level of RFC2 ubiquitination. Our study offers a potential novel target for the early diagnosis and treatment of GC.
참고문헌 (34)
- Niu Y, "Physcion 8-O-β-glucopyranoside induced ferroptosis via regulating miR-103a-3p", GLS2 axis in gastric cancer, 2019, pp.237, 116893~
- Smyth EC, "Gastric cancer", Lancet(London, England), 396, pp.635~648 (2020)
- Karimi P, "Gastric cancer : descriptive epidemiology, risk factors, screening, and prevention", Cancer Epidemiol. Biomarkers Prev, 23, pp.700~713 (2014)
- "Der Internist", 2014
- Necula L, "Recent advances in gastric cancer early diagnosis", World J. Gastroenterol, 25, pp.2029~2044 (2019)
- Li B, "circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity", Nat. Commun, 12, pp.295~ (2021)
- Xia Y, "CircFAM73A promotes the cancer stem cell-like properties of gastric cancer through the miR-490-3p", HMGA2 positive feedback loop and HNRNPK-mediated β-catenin stabilization, 2021, pp.40, 103~
- Cao J, "Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2", β-catenin pathway, 2021, pp.40, 6~
- Dai X, "Circular RNA circFGD4 suppresses gastric cancer progression via modulating miR-532-3p", APC, Clin. Sci. London, pp.2020, 134[DOI]
- Wei T, "Circular RNA expression profiling identifies specific circular RNAs in tongue squamous cell carcinoma", Mol. Med. Rep, 21, pp.1727~1738 (2020)
- Rong L, "COL1A2 is a novel biomarker to improve clinical prediction in human gastric cancer : Integrating bioinformatics and meta-analysis", Pathol. Oncol. Res, 24, pp.129~134 (2018)
- Ao R, "Silencing of COL1A2, COL6A3, and THBS2 inhibits gastric cancer cell proliferation, migration, and invasion while promoting apoptosis through the PI3k-Akt signaling pathway", J. Cell. Biochem, 119, pp.4420~4434 (2018)
- Hong M, "RNA sequencing : new technologies and applications in cancer research", J. Hematol. Oncol, 13, pp.166~ (2020)
- Tao Z, "Microarray bioinformatics in cancer-a review", J. BUON, 22, pp.838~843 (2017)
- Chen Y, "Lnc-M2 controls M2 macrophage differentiation via the PKA", CREB pathway, 2020, pp.124, 142~152
- Yuan S, "LncRNA UCID Promotes hepatocellular carcinoma metastasis via stabilization of snail", OncoTargets Ther, 14, pp.725~736 (2021)
- Hu YP, "LncRNA-HGBC stabilized by HuR promotes gallbladder cancer progression by regulating miR-502-3p", SET, Mol. Cancer, pp.2019, 18[DOI]
- Wang LQ, "LncRNA-Fendrr protects against the ubiquitination and degradation of NLRC4 protein through HERC2 to regulate the pyroptosis of microglia", Mol. Med, 27, pp.39~ (2021)
- Sun Z, "YAP1-induced MALAT1 promotes epithelial-mesenchymal transition and angiogenesis by sponging miR-126-5p in colorectal cancer", Oncogene, 38, pp.2627~2644 (2019)
- Zhang Y, "CircDIDO1 inhibits gastric cancer progression by encoding a novel DIDO1-529aa protein and regulating PRDX2 protein stability", Mol. Cancer, 20, pp.101~ (2021)
- Qu J, "CircFLNA acts as a sponge of miR-646 to facilitate the proliferation, metastasis, glycolysis, and apoptosis inhibition of gastric cancer by targeting PFKFB2", Cancer Manag. Res, 12, pp.8093~8103 (2020)
- Wang Z, "CXCL1 from tumor-associated lymphatic endothelial cells drives gastric cancer cell into lymphatic system via activating integrin β1", FAK, Cancer Lett, pp.2017, 385[DOI]
- Lee SW, "Synergistic triad epistasis of epigenetic H3K27me modifier genes, EZH2, KDM6A, and KDM6B, in gastric cancer susceptibility", Gastric Cancer, 22, pp.640~644 (2019)
- Gou WF, "ING5 suppresses proliferation, apoptosis, migration and invasion, and induces autophagy and differentiation of gastric cancer cells : a good marker for carcinogenesis and subsequent progression", Oncotarget, 6, pp.19552~19579 (2015)
- Liu X, "α-Actinin-4 promotes metastasis in gastric cancer", Lab. Invest, 97, pp.1084~1094 (2017)
- Cheng LL, "TP53 genomic status regulates sensitivity of gastric cancer cells to the histone methylation inhibitor 3-deazaneplanocin A(DZNep)", Clin. Cancer Res, 18, pp.4201~4212 (2012)
- Zeng Z, "Prognostic significance of USP10 as a tumor-associated marker in gastric carcinoma", Tumour Biol, 35, pp.3845~3853 (2014)
- Li Y, "Multifaceted regulation and functions of replication factor C family in human cancers", Am. J. Cancer Res, 8, pp.1343~1355 (2018)
- Zhu H, "USP10 Promotes proliferation of hepatocellular carcinoma by deubiquitinating and stabilizing YAP", TAZ, 2020, pp.80, 2204~2216
- Sun J, "USP10 inhibits lung cancer cell growth and invasion by upregulating PTEN", Mol. Cell. Bochem, 441, pp.1~7 (2018)
- Ko A, "Oncogene-induced senescence mediated by c-Myc requires USP10dependent deubiquitination and stabilization of p14ARF", Cell Death Differ, 25, pp.1050~1062 (2018)
- Ouyang SW, "USP10 regulates Musashi-2 stability via deubiquitination and promotes tumour proliferation in colon cancer", FEBS Lett, 593, pp.406~413 (2019)
- Hu T, "RFC2, a direct target of miR-744, modulates the cell cycle and promotes the proliferation of CRC cells", J. Cell. Physiol, 235, pp.8319~8333 (2020)
- Ji Z, "Up-regulated RFC2 predicts unfavorable progression in hepatocellular carcinoma", Hereditas, 158, pp.17~ (2021)