The Circular RNA Circ_0043947 Promoted Gastric Cancer Progression by Sponging miR-384 to Regulate CREB1 Expression
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Background/Aims: The occurrence and development of circular RNAs in gastric cancer (GC) has attracted increasing attention. This study focused on investigating the biological role and molecular mechanism of circ_0043947 in GC. Methods: The expression levels of circ_0043947, miR-384 and CAMP response element binding protein (CREB1) were determined by quantitative real-time polymerase chain reaction or Western blotting. Cell proliferation, migration, and invasion, the cell cycle and apoptosis were determined using a cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, colony formation assay, wound healing assay, transwell assay, and flow cytometry assay. The interaction between miR-384 and circ_0043947 or CREB1 was verified by dual-luciferase reporter assay and RNA pull-down assay. The in vivo assay was conducted using a xenograft mouse model. Results: Circ_0043947 and CREB1 expression levels were significantly upregulated, whereas miR-384 expression levels were downregulated in GC tissues and cells. Functionally, knockdown of circ_0043947 inhibited cell proliferation, migration and invasion and induced G0/G1 phase arrest and apoptosis in vitro. Circ_0043947 could upregulate CREB1 expression by directly sponging miR-384. Rescue experiments showed that a miR-384 inhibitor significantly reversed the inhibitory effect of si-circ_0043947 on GC progression, and CREB1 overexpression significantly reversed the inhibitory effect of miR-384 mimics on the progression of GC cells. Furthermore, silencing of circ_0043947 inhibited tumor growth in vivo. Conclusions: Circ_0043947 acted as an oncogenic factor in GC to mediate GC cell proliferation, migration, and invasion, the cell cycle and apoptosis by regulating the miR-384/CREB1 axis. Circ_0043947 may be a potential target for GC diagnosis and therapy.
Abstract
Background/Aims: The occurrence and development of circular RNAs in gastric cancer (GC) has attracted increasing attention. This study focused on investigating the biological role and molecular mechanism of circ_0043947 in GC. Methods: The expression levels of circ_0043947, miR-384 and CAMP response element binding protein (CREB1) were determined by quantitative real-time polymerase chain reaction or Western blotting. Cell proliferation, migration, and invasion, the cell cycle and apoptosis were determined using a cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, colony formation assay, wound healing assay, transwell assay, and flow cytometry assay. The interaction between miR-384 and circ_0043947 or CREB1 was verified by dual-luciferase reporter assay and RNA pull-down assay. The in vivo assay was conducted using a xenograft mouse model. Results: Circ_0043947 and CREB1 expression levels were significantly upregulated, whereas miR-384 expression levels were downregulated in GC tissues and cells. Functionally, knockdown of circ_0043947 inhibited cell proliferation, migration and invasion and induced G0/G1 phase arrest and apoptosis in vitro. Circ_0043947 could upregulate CREB1 expression by directly sponging miR-384. Rescue experiments showed that a miR-384 inhibitor significantly reversed the inhibitory effect of si-circ_0043947 on GC progression, and CREB1 overexpression significantly reversed the inhibitory effect of miR-384 mimics on the progression of GC cells. Furthermore, silencing of circ_0043947 inhibited tumor growth in vivo. Conclusions: Circ_0043947 acted as an oncogenic factor in GC to mediate GC cell proliferation, migration, and invasion, the cell cycle and apoptosis by regulating the miR-384/CREB1 axis. Circ_0043947 may be a potential target for GC diagnosis and therapy.
참고문헌 (33)
- Sung H, "Global cancer statistics 2020 : GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries", CA Cancer J Clin, 71, pp.209~249 (2021)
- Cao W, "Changing profiles of cancer burden worldwide and in China : a secondary analysis of the global cancer statistics 2020", Chin Med J(Engl), 134, pp.783~791 (2021)
- Allemani C, "Global surveillance of trends in cancer survival 2000-14(CONCORD-3) : analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries", Lancet, 391, pp.1023~1075 (2018)
- Wang TT, "Tumour-activated neutrophils in gastric cancer foster immune suppression and disease progression through GM-CSF-PD-L1 pathway", Gut, 66, pp.1900~1911 (2017)
- Qu S, "The emerging landscape of circular RNA in life processes", RNA Biol, 14, pp.992~999 (2017)
- Li J, "Circular RNAs in cancer : biogenesis, function, and clinical significance", Trends Cancer, 6, pp.319~336 (2020)
- Zhou WY, "Circular RNA : metabolism, functions and interactions with proteins", Mol Cancer, 19, pp.172~ (2020)
- Hu ZQ, "Circular RNA sequencing identifies CircASAP1 as a key regulator in hepatocellular carcinoma metastasis", Hepatology, 72, pp.906~922 (2020)
- Chen LY, "The circular RNA circ-ERBIN promotes growth and metastasis of colorectal cancer by miR-125a-5p and miR-138-5p", 4EBP-1 mediated capindependent HIF-1α translation, 2020, pp.19, 164~
- Zhang N, "Circular RNA circSATB2promotes progression of non-small cell lung cancer cells", Mol Cancer, 19, pp.101~ (2020)
- Cai H, "Circular RNA hsa_circ_0000263 participates in cervical cancer development by regulating target gene of miR-150-5p", J Cell Physiol, 234, pp.11391~11400 (2019)
- Zhang X, "Circular RNA circNRIP1acts as a microRNA-149-5p sponge to promote gastric cancer progression via the AKT1", mTOR pathway, 2019, pp.18, 20~
- Gong Y, "Construction of a circRNA-miRNA-mRNA network based on differentially co-expressed circular RNA in gastric cancer tissue and plasma by bioinformatics analysis", World J Surg Oncol, 20, pp.34~ (2022)
- Dudekula DB, "CircInteractome : a web tool for exploring circular RNAs and their interacting proteins and microRNAs", RNA Biol, 13, pp.34~42 (2016)
- Witkos TM, "Practical aspects of microRNA target prediction", Curr Mol Med, 11, pp.93~109 (2011)
- Zhong BZ, "Effects of miR-384 and miR-134-5p acting on YY1 signaling transduction on biological function of gastric cancer cells", Onco Targets Ther, 13, pp.9631~9641 (2020)
- Liu P, "Circular RNA-hsa-circ-0000670 promotes gastric cancer progression through the microRNA-384", SIX4axis, 2020, pp.394, 112141~
- Zheng T, "Systematical analysis reveals a strong cancer relevance of CREB1-regulated genes", Cancer Cell Int, 21, pp.530~ (2021)
- Yan L, "A CREB1", miR-433 reciprocal feedback loop modulates proliferation and metastasis in colorectal cancer, 2018, pp.10, 3774~3793
- Guo L, "CREB1, a direct target of miR-122, promotes cell proliferation and invasion in bladder cancer", Oncol Lett, 16, pp.3842~3848 (2018)
- Wang W, "The epigenetic silencing of microRNA-433 facilitates the malignant phenotypes of non-small cell lung cancer by targeting CREB1", Am J Transl Res, 13, pp.12302~12317 (2021)
- Han J, "Norepinephrine-CREB1-miR-373 axis promotes progression of colon cancer", Mol Oncol, 14, pp.1059~1073 (2020)
- Wang YW, "High expression of cAMPresponsive element-binding protein 1(CREB1)is associated with metastasis, tumor stage and poor outcome in gastric cancer", Oncotarget, 6, pp.10646~10657 (2015)
- Zhang J, "PODXL, negatively regulated by KLF4, promotes the EMT and metastasis and serves as a novel prognostic indicator of gastric cancer", Gastric Cancer, 22, pp.48~59 (2019)
- Huang A, "Circular RNA-protein interactions : functions, mechanisms, and identification", Theranostics, 10, pp.3503~3517 (2020)
- Alagia A, "siRNA and RNAi optimization", Wiley Interdiscip Rev RNA, 7, pp.316~329 (2016)
- Zhang MM, "The growth of siRNA-based therapeutics : updated clinical studies", Biochem Pharmacol, 189, pp.114432~ (2021)
- O’Brien J, "Overview of microRNA biogenesis, mechanisms of actions, and circulation", Front Endocrinol(Lausanne), 9, pp.402~ (2018)
- Zheng J, "MicroRNA-4651 targets bromodomain-containing protein 4 to inhibit non-small cell lung cancer cell progression", Cancer Lett, 476, pp.129~139 (2020)
- Song L, "miR-144-3p facilitates nasopharyngeal carcinoma via crosstalk with PTEN", J Cell Physiol, 234, pp.17912~17924 (2019)
- Guo Q, "MiR-384 induces apoptosis and autophagy of non-small cell lung cancer cells through the negative regulation of Collagen α-1(X)chain gene", Biosci Rep, 39, pp.BSR20181523~ (2019)
- Wang YX, "MiR-384inhibits the proliferation of colorectal cancer by targeting AKT3", Cancer Cell Int, 18, pp.124~ (2018)
- Tan Y, "MiR-384 inhibits malignant biological behavior such as proliferation and invasion of osteosarcoma by regulating IGFBP3", Technol Cancer Res Treat, 19, pp.1533033820909125~ (2020)