uc.454 Inhibited Growth by Targeting Heat Shock Protein Family A Member 12B in Non-Small-Cell Lung Cancer.

uc.454 Inhibited Growth by Targeting Heat Shock Protein Family A Member 12B in Non-Small-Cell Lung Cancer.
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uc.454 通过靶向热休克蛋白家族 A 成员 12B 抑制非小细胞肺癌的生长

DOI:
10.1016/j.omtn.2018.05.004
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发表时间:
2018-09-07
期刊:
Molecular therapy. Nucleic acids
影响因子:
--
通讯作者:
Shi M
Shi M
中科院分区:
其他
文献类型:
--
作者:
Zhou J;Wang C;Gong W;Wu Y;Xue H;Jiang Z;Shi M

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转录超常服务区(T-UCR)被归类为长非编码RNAs(LNC-RNAs),是一种长度大于200-nT的转录本,没有蛋白质编码能力。以往的研究表明,T-UCR是一种新的癌基因,抑癌基因参与了肿瘤的发生和发展。然而,T-UCRs在肺癌(LC)中的临床病理意义和调控机制尚不清楚。我们发现uc.454在非小细胞LC(NSCLC)组织和LC细胞系中均下调,并且uc.454下调与肿瘤大小和肿瘤分期较晚期有关。转染uc.454可明显诱导SPC-A-1和NCI-H_2170 LC细胞的凋亡并抑制其增殖。以上结果提示uc.454在LC中具有抑制作用。通过双荧光素酶报告基因分析,热休克蛋白家族A成员12B(HSPA12B)蛋白被uc.454在转录后水平负调控,并影响Bcl2家族成员的表达,最终诱导LC细胞凋亡。UC.454/HSPA12B轴进一步加深了我们对肿瘤细胞凋亡分子机制的理解,这可能成为肺癌的治疗靶点。
Transcribed ultraconserved regions (T-UCRs) classified as long non-coding RNAs (Lnc-RNAs) are transcripts longer than 200-nt RNA with no protein-coding capacity. Previous studies showed that T-UCRs serve as novel oncogenes, or tumor suppressors are involved in tumorigenesis and cancer progressive. Nevertheless, the clinicopathologic significance and regulatory mechanism of T-UCRs in lung cancer (LC) remain largely unknown. We found that uc.454 was downregulated in both non-small-cell LC (NSCLC) tissues and LC cell lines, and the downregulated uc.454 is associated with tumor size and tumors with more advanced stages. Transfection with uc.454 markedly induced apoptosis and inhibited cell proliferation in SPC-A-1 and NCI-H2170 LC cell lines. Above results suggested that uc.454 played a suppressive role in LC. Heat shock protein family A member 12B (HSPA12B) protein was negatively regulated by uc.454 at the posttranscriptional level by dual-luciferase reporter assay and affected the expressions of Bcl-2 family members, which finally induced LC apoptosis. The uc.454/HSPA12B axis furthers our understanding of the molecular mechanisms involved in tumor apoptosis, which may potentially serve as a therapeutic target for lung carcinoma.
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