The Anti-tumor Mechanisms Study Of Oxymatrine On Gastric Carcinoma Mediated By LncRNA AK023391

Background Patients with gastric cancer commonly have a poor prognosis,owing to its invasiveness and distant metastasis.Recent studies have confirmed the pivotal role of long non-coding RNAs(lnc RNAs)in tumorigenesis and the progression of malignant tumors,including gastric cancer.Our previous study found that lnc RNA AK023391 was overexpressed in gastric cancer and oxymatrine had a good anti-gastric cancer effect.In this study,we investigated the expression of lnc RNA AK023391 in gastric cancer tissues and cell lines and observed its effect on the biological behavior of gastric cancer cells.To further explore AK023391 mediated molecular mechanism of traditional Chinese medicine oxymatrine regulating gastric cancer proliferation and invasion,provide a new drug target for the treatment of gastric cancer.Methods 1.RNA fluorescence in situ hybridization(FISH)was used to investigate the association between AK023391 expression and the clinicopathological characteristics and prognosis of patients with gastric cancer.q RT-PCR assay was used to detect the expression of lnc RNA AK023391 in gastric cancer cell lines and normal gastric mucosa.2.A series of in vitro assays such as cell proliferation,migration and invasion assaysand in vivo assay were used to observe the functions of lnc RNA AK023391 in gastric cancer cells after transfection.3.The Whole Human Genome Oligo Microarray,bioinformatic analysis,western blotting,and immunochemistry were carried out to verify the regulation of AK023391 and its downstream PI3K/Akt signaling pathway.4.Overexpression of AK023391,and MTT,Transwell,Western blot assays were used to detect the relationship between oxymatrine and lnc RNA AK023391 on gastric cancer cells.Results: 1.Expression of lnc RNA AK023391 was significantly upregulated in gastric cancer samples and cell lines compared with adjacent normal tissues,Expression of lnc RNA AK023391 was positively correlated with poor survival in patients with gastric cancer.The multivariate Cox regression model revealed that AK023391 expression acted as an independent prognostic factor for survival in patients with gastric cancer.2.In vitro,CCK-8 and colony formation assays showed that it can inhibit the proliferation of gastric cancer cells.Transwell assay illustrated that sh-AK023391 can reduce the invasion ability of gastric cancer cell.Wound healing assay showed that the group of sh-AK023391 has the ability to reduce gastric cancer cell migration.Meanwhile,nude mice tumorigenicity results demonstrated that sh-AK023391 can inhibit the tumor growth in vivo.3.The Whole Human Genome Oligo Microarray was used to detect the differentiallexpressed genes,we found that about a total of 394 genes were significantly up-regulated,676 genes were significantly down-regulated.Then pathway analysis were performed in the standard enrichment computation method,which found that the PI3 K / AKT signaling pathway was significantly enriched,suggesting that this pathway may be the pathway of lnc RNA AK023391 mediated and it was validated by Western blot assay.4.Oxymatrine could inhibit the expression of lnc RNA AK023391,while overexpression of AK023391,the proliferation and invasion ability of gastric cancer cell was weakened when treated with oxymatrine.So we inferred that the mechanism of oxymatrine by which it focus on the gastric cancer proliferation and invasion may be related to that it could downregulated the expression of lnc RNA AK023391.Conclusion: Lnc RNA AK023391 is overexpressed both in gastric cancer tissues and gastric cancer cell lines and it can be used as an independent prognostic factor in patients with gastric cancer,it also can promote the proliferation and invasion of gastric cancer cells.Lnc RNA AK023391 regulates the biological behavior of gastric cancer cells mainly through the PI3 K / AKT signaling pathway.And oxymatrine inhibits the proliferation and invasion of gastric cancer cells may partly by inhibiting the expression of AK023391.This provides some theoretical and experimental basis for the treatment of gastric cancer.