| BackgroundGastrointestinal stromal tumors(GIST)is a type of tumor that originates in the mesenchymal tissues of the gastrointestinal tract.The tumor cells have the tyrosine kinase receptor c-KIT gene(ey: CD117)and the bone marrow stem cell antigen CD34 positive expression,and the annual incidence rate of GIST is about 10-20/100 million,accounting for 1-3% of gastrointestinal malignant tumors.It is commonly found in the middle-aged and elderly people and seriously threatens people’s health.Long noncoding RNA(LncRNA)refers to RNA that is greater than 200 nucleotides in length and generally has no protein-coding function.Many studies have confirmed that LncRNA is abnormally expressed in a variety of tumors,plays an important regulatory role in tumorigenesis and development,and is an important factor in tumorigenesis.Studies have found that it is inseparable from the development of gastrointestinal stromal tumors.This study found that the expression of LncRNA HOTAIR(The long noncoding RNA homeobox transcript antisense intergenic RNA)is abnormally increased in gastrointestinal stromal tumor tissues,and also found that HOTAIR is highly expressed in gastrointestinal stromal tumor cells,and can promote tumor growth,but the specific mechanism of HOTAIR involved in the occurrence and development of gastrointestinal stromal tumors is not fully understood.Lnc Base Predicted v.2 predicts that HOTAIR has a targeted binding site with miR-134-5p.miR-134-5p can be used as a tumor suppressor and can inhibit tumor growth and metastasis.Starbase2.0 predicts that FGF2(Fibroblast growth factor 2)has a targeted binding site with miR-134-5p,and FGF2 expression increases in gastrointestinal stromal tumors and regulates the biological behavior of gastrointestinal stromal tumor cells.However,whether HOTAIR can participate in the occurrence and development of gastrointestinal stromal tumors by regulating the expression of miR-134-5p/FGF2 is not yet known.ObjectiveThis study analyzed the effect of knockdown of HOTAIR on the biological behavior of gastrointestinal stromal tumor cells,and explored its regulatory effect on miR-134-5p/FGF2,laying an experimental foundation for further revealing the pathogenesis of gastrointestinal stromal tumors.At the same time,it provides a theoretical basis for clinical targeted therapy of gastrointestinal stromal tumors.Methods1 qRT-PCR and Western blot detection the expression levels of HOTAIR,miR-134-5p,FGF2 of gastrointestinal stromal tumor tissue,adjacent tissues and human normal gastric mucosal epithelial cells RGM-1,gastrointestinal stromal tumor cell lines GIST-430,GIST-882,GIST-T1 cells;2 si-HOTAIR,anti-miR-134-5p,miR-134-5p mimics,and FGF2 overexpression vectors were transfected into gastrointestinal stromal tumor GIST-882 and GIST-T1 cells,respectively;Using Ed U and MTT experiments to detect the proliferation ability of GIST cells;Apoptosis was detected by flow cytometry.GIST cell invasion and migration were detected by transwell assay and scratch assay;Using western blot to detect proliferation and migration related protein(Cyclin D1,MMP9)expression;Dual-luciferase reporter experiment was used to detect the regulatory relationship between HOTAIR and miR-134-5p,and the targeting relationship between miR-134-5p and FGF2.Results1.In gastrointestinal stromal tumor tissues and cell lines,the expression of HOTAIR is increased compared with normal tissues and cells;knocking down HOTAIR can inhibit the proliferation,migration and invasion of GIST cells,and promote cell apoptosis.2.Inhibiting the expression of miR-134-5p can restore the effect of knockdown of HOTAIR on the proliferation,migration,invasion and apoptosis of gastrointestinal stromal tumor cells.3.HOTAIR can target regulate the expression of miR-134-5p,and miR-134-5p can target regulate the expression of FGF2.ConclusionsLncRNA HOTAIR promotes FGF2 expression by lowering miR-134-5p,thereby promoting the proliferation,invasion and migration of gastrointestinal mesothelioma cells. |
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