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长链非编码 RNA FAM84B-AS 通过抑制 FAM84B 表达促进胃癌对铂类药物耐药。

Long non-coding RNA FAM84B-AS promotes resistance of gastric cancer to platinum drugs through inhibition of FAM84B expression.

机构信息

Department of Gastrointestinal Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, PR China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, PR China.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, PR China.

出版信息

Biochem Biophys Res Commun. 2019 Feb 12;509(3):753-762. doi: 10.1016/j.bbrc.2018.12.177. Epub 2019 Jan 9.

DOI:10.1016/j.bbrc.2018.12.177
PMID:30638658
Abstract

PURPOSE

To investigate the expression and significance of the long non-coding RNA (lncRNA) FAM84B-AS in gastric cancer tissues and its effect on platinum drug resistance in gastric cancer.

METHODS

(1) The expression of FAM84B-AS was detected in samples from 228 cases of fresh gastric cancer to analyze its association with clinical data and gastric cancer prognosis. (2) An lncRNA interference cell line model was established and used to study the effects of FAM84B-AS on the malignant biological behaviors of gastric cancer cells and platinum drug resistance at the cellular level. (3) The mechanisms underlying the effect of FAM84B-AS on gastric cancer were investigated using Western blotting.

RESULTS

(1) FAM84B-AS was closely associated with the differentiation level, T stage, and N stage of gastric cancer and could be used as an independent risk factor of the prognosis of gastric cancer. (2) FAM84B-AS interference significantly inhibited the proliferation and invasion abilities of gastric cancer cells and significantly increased the percentage of apoptosis. FAM84B-AS could partially restore the sensitivity of drug resistant cells to platinum drugs. The above results were also confirmed in in vivo studies. (3) Western blot results demonstrated that FAM84B-AS interference could activate apoptosis signaling pathways in gastric cancer cells to promote apoptosis in gastric cells.

CONCLUSION

FAM84B-AS could be used as a molecular marker of the malignancy of gastric cancer and offers a certain predictive function for gastric cancer prognosis. FAM84B-AS promotes gastric cancer proliferation through inhibition of apoptosis signaling pathways and promotes drug resistance of gastric cancer cells to platinum drugs through its apoptosis-inhibiting functions.

摘要

目的

研究长链非编码 RNA(lncRNA)FAM84B-AS 在胃癌组织中的表达及意义及其对胃癌铂类耐药的影响。

方法

(1)检测 228 例新鲜胃癌组织中 FAM84B-AS 的表达,分析其与临床资料及胃癌预后的关系。(2)构建 lncRNA 干扰细胞系模型,研究 FAM84B-AS 对胃癌细胞恶性生物学行为及铂类耐药性的影响。(3)采用 Western blot 法探讨 FAM84B-AS 对胃癌作用的机制。

结果

(1)FAM84B-AS 与胃癌的分化程度、T 分期、N 分期密切相关,可作为胃癌预后的独立危险因素。(2)FAM84B-AS 干扰显著抑制胃癌细胞的增殖和侵袭能力,显著增加细胞凋亡率。FAM84B-AS 可部分恢复耐药细胞对铂类药物的敏感性。体内研究也证实了上述结果。(3)Western blot 结果表明,FAM84B-AS 干扰可激活胃癌细胞凋亡信号通路,促进胃癌细胞凋亡。

结论

FAM84B-AS 可作为胃癌恶性程度的分子标志物,对胃癌的预后具有一定的预测作用。FAM84B-AS 通过抑制凋亡信号通路促进胃癌细胞增殖,并通过抑制凋亡功能促进胃癌细胞对铂类药物的耐药性。

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