MBNL3 Acts as a Target of miR-302e to Facilitate Cell Proliferation, Invasion and Angiogenesis of Gastric Adenocarcinoma via AKT/VEGFA Pathway
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Gastric adenocarcinoma (GAC) is a common, malignant type of tumor in human, and is accompanied with higher mortality. Muscleblind-like 3 (MBNL3) was found to be a pivotal participator in aggravating this cancer’s progression. However, the regulatory effects of MBNL3 on GAC development have not been investigated. We therefore sought to study the functions of MBNL3 in GAC progression. In this study, it was demonstrated that MBNL3 exhibited higher expression, and GAC patients with higher MBNL3 expression had poor prognosis. Overexpression of MBNL3 facilitated, and knockdown of MBNL3 suppressed cell proliferation, invasion, and angiogenesis in GAC. Further experiments showed that miR-302e targets MBNL3. Rescue assays then uncovered that the miR-302e/MBNL3 axis aggravated GAC progression. In addition, MBNL3 activated the AKT/VEGFA pathway, and the suppressive regulatory impacts of MBNL3 knockdown on GAC cell proliferation, invasion, and angiogenesis could be rescued after 740 Y-P treatment. Through in vivo assay, it was proved that MBNL3 accelerated tumor growth in vivo. In conclusion, MBNL3 acted as a target of miR-302e to facilitate cell proliferation, invasion, and angiogenesis of gastric adenocarcinoma through the AKT/ VEGFA pathway. Our findings illustrate that MBNL3 may be an available bio-target for GAC treatment.
Abstract
Gastric adenocarcinoma (GAC) is a common, malignant type of tumor in human, and is accompanied with higher mortality. Muscleblind-like 3 (MBNL3) was found to be a pivotal participator in aggravating this cancer’s progression. However, the regulatory effects of MBNL3 on GAC development have not been investigated. We therefore sought to study the functions of MBNL3 in GAC progression. In this study, it was demonstrated that MBNL3 exhibited higher expression, and GAC patients with higher MBNL3 expression had poor prognosis. Overexpression of MBNL3 facilitated, and knockdown of MBNL3 suppressed cell proliferation, invasion, and angiogenesis in GAC. Further experiments showed that miR-302e targets MBNL3. Rescue assays then uncovered that the miR-302e/MBNL3 axis aggravated GAC progression. In addition, MBNL3 activated the AKT/VEGFA pathway, and the suppressive regulatory impacts of MBNL3 knockdown on GAC cell proliferation, invasion, and angiogenesis could be rescued after 740 Y-P treatment. Through in vivo assay, it was proved that MBNL3 accelerated tumor growth in vivo. In conclusion, MBNL3 acted as a target of miR-302e to facilitate cell proliferation, invasion, and angiogenesis of gastric adenocarcinoma through the AKT/ VEGFA pathway. Our findings illustrate that MBNL3 may be an available bio-target for GAC treatment.
참고문헌 (28)
- Machlowska J, "Gastric cancer : epidemiology, risk factors, classification, genomic characteristics and treatment strategies", Int. J. Mol. Sci, 21, pp.4012~ (2020)
- Smyth EC, "Gastric cancer", Lancet, 396, pp.635~648 (2020)
- Cerrato-Izaguirre D, "Mutational landscape of gastric adenocarcinoma in Latin America : a genetic approach for precision medicine", Genes Dis, 9, pp.928~940 (2022)
- Hoshi H, "Management of gastric adenocarcinoma for general surgeons", Surg. Clin. North Am, 100, pp.523~534 (2020)
- Ajani JA, "Gastric adenocarcinoma", Nat. Rev. Dis. Primers, 3, pp.17036~ (2017)
- Sun X, "Nanog-mediated stem cell properties are critical for MBNL3-associated paclitaxel resistance of ovarian cancer", J. Biochem, 169, pp.747~756 (2021)
- Oladimeji PO, "KANSL2 and MBNL3 are regulators of pancreatic ductal adenocarcinoma invasion", Sci. Rep, 10, pp.1485~ (2020)
- Yu Z, "LncRNA SBF2-AS1 affects the radiosensitivity of non-small cell lung cancer via modulating microRNA-302a", MBNL3 axis, 2020, pp.19, 300~316
- Yuan JH, "The MBNL3 splicing factor promotes hepatocellular carcinoma by increasing PXN expression through the alternative splicing of lncRNA-PXN-AS1", Nat. Cell Biol, 19, pp.820~832 (2017)
- Revathidevi S, "Akt in cancer : mediator and more", Semin. Cancer Biol, 59, pp.80~91 (2019)
- Xu Z, "Targeting PI3K", AKT, Appl. Microbiol. Biotechnol, pp.2020, 104[DOI]
- Baghery Saghchy Khorasani A, "The PI3K", Akt, Eur. J. Pharmacol, pp.2021, 898[DOI]
- Fattahi S, "PI3K", AKT, Life Sci, pp.2020, 262[DOI]
- Viallard C, "Tumor angiogenesis and vascular normalization : alternative therapeutic targets", Angiogenesis, 20, pp.409~426 (2017)
- Olejarz W, "Exosomes in angiogenesis and anti-angiogenic therapy in cancers", Int. J. Mol. Sci, 21, pp.5840~ (2020)
- Zhang S, "MicroRNA-574-5p in gastric cancer cells promotes angiogenesis by targeting protein tyrosine phosphatase non-receptor type 3(PTPN3)", Gene, 733, pp.144383~ (2020)
- Chen JJ, "JP3, an antiangiogenic peptide, inhibits growth and metastasis of gastric cancer through TRIM25", SP1, J. Exp. Clin. Cancer Res, pp.2020, 39[DOI]
- Lv WL, "PAX3 silencing suppresses gastric cancer proliferation and angiogenesis via MET", PI3K signaling, 2020, pp.67, 304~311
- Han X, "Knockdown of mediator complex subunit 27 suppresses gastric cancer cell metastasis and angiogenesis via Wnt", β-catenin pathway, 2022, pp.79, 101973~
- Zhu H, "MiR-877 suppresses gastric cancer progression by downregulating AQP3", J. Int. Med. Res, 48, pp.300060520903661~ (2020)
- Liu H, "miR-613 inhibits Warburg effect in gastric cancer by targeting PFKFB2", Biochem. Biophys. Res. Commun, 515, pp.37~43 (2019)
- Zhang H, "MiR-489 inhibited the development of gastric cancer via regulating HDAC7and PI3K", AKT pathway, 2020, pp.18, 73~
- Xie Y, "miR-302e suppresses glioma progression by targeting VEGFA", Cancer Manag. Res, 12, pp.10965~10974 (2020)
- Li D, "Long noncoding RNA FGD5-AS1 promotes colorectal cancer cell proliferation, migration, and invasion through upregulating CDCA7 via sponging miR-302e", In Vitro Cell. Dev. Biol. Anim, 55, pp.577~585 (2019)
- Chen B, "CXCL1 regulated by miR-302e is involved in cell viability and motility of colorectal cancer via inhibiting JAK-STAT signaling pathway", Front. Oncol, 10, pp.577229~ (2020)
- Wu S, "ORAI2 promotes gastric cancer tumorigenicity and metastasis through PI3K", Akt signaling and MAPK-dependent focal adhesion disassembly, 2021, pp.81, 986~1000
- Zhang H, "LAMB3 mediates apoptotic, proliferative, invasive, and metastatic behaviors in pancreatic cancer by regulating the PI3K", Akt signaling pathway, 2019, pp.10, 230~
- Zhang J, "Nucleoporin 37 promotes the cell proliferation, migration, and invasion of gastric cancer through activating the PI3K", AKT, In Vitro Cell. Dev. Biol. Anim, pp.2021, 57[DOI]