LncRNA HOTAIR、HOTTIP及其下游HOXD10、HOXA13基因在肺癌中的表达研究
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摘要
目的探讨HOTAIR和HOTTIP及其下游HOXD10和HOXA13基因在肺癌中的表达特征以及相互调控的关系.方法选择47例肺癌患者并收集癌组织和癌旁正常组织,利用TRIzol提取总RNA,实时荧光定量PCR检测基因相对表达量.结果 HOTAIR在癌组织中的相对表达量(4.12±4.58),显著低于癌旁正常组织(7.43±4.20),(P<0.01),HOXA13在癌组织中的相对表达量(8.64±1.21),显著降低低于癌旁正常组织(9.43±1.58),(P<0.01),其他两个基因表达无显著变化.在有淋巴转移的个体中,癌组织中HOXD10 mRNA表达为(9.01±1.22),显著高于无转移的患者(7.81±2.15),(P=0.02).HOTTIP与下游HOXA13基因RNA在癌组织(r=0.78,P=0.00)和癌旁正常组织(r=0.70,P<0.01)中均存在正相关关系;HOTAIR与下游HOXD10基因mRNA在癌旁正常组织中成正相关(r=0.37,P<0.01),在癌组织中却不存在相关关系(r=0.12,P=0.47).结论提示在肺癌中HOTTIP与HOXA13调控关系正常;HOTAIR在癌组织中表达降低,且可能丧失对下游基因HOXD10的正常调控.
Objective To study the expression characteristics of HOTAIR and HOTTIP and their downstream HOXD10 and HOXA13 genes in lung cancer,as well as the relationship of mutual regulation.Methods We selected 47 patients with lung cancer and collected their cancer tissue and adjacent normal tissue,then used TRIzol to extract total RNA and real-time quantitative PCR to detect relative gene expression levels. Results HOTAIR and HOXA13 relative expression levels in cancer tissues were significantly lower than in adjacent normal tissues(4.12±4.58) vs(7.43±4.20) P < 0.01,(8.64±1.21) vs(9.43±1.58) P < 0.01),and the other three genes expressions were not significantly changed. HOXD10 mRNA expression levels in the cancer tissue of individuals with lymph node were significantly higher than patients without lymph node(9.01±1.22) vs(7.81±2.15),P =0.02). There were positive correlation relationships between the expressions of HOTTIP and its downstream gene HOXA13 mRNA in cancer tissue(r = 0.78,P < 0.01) and adjacent normal tissue(r = 0.70,P < 0.01);the HOTAIR and its downstream HOXD10 gene mRNA in adjacent normal tissue were positively related(r = 0.37,P =0.01),but not correlated in cancer tissues(r = 0.12,P = 0.47). Conclusions The regulation between HOTTIP and HOXA13 is normal in lung cancer. The expression of HOTAIR decreases in cancer tissues,and HOTAIR may lose the normal regulation of downstream genes of HOXD10.
Objective To study the expression characteristics of HOTAIR and HOTTIP and their downstream HOXD10 and HOXA13 genes in lung cancer,as well as the relationship of mutual regulation.Methods We selected 47 patients with lung cancer and collected their cancer tissue and adjacent normal tissue,then used TRIzol to extract total RNA and real-time quantitative PCR to detect relative gene expression levels. Results HOTAIR and HOXA13 relative expression levels in cancer tissues were significantly lower than in adjacent normal tissues(4.12±4.58) vs(7.43±4.20) P < 0.01,(8.64±1.21) vs(9.43±1.58) P < 0.01),and the other three genes expressions were not significantly changed. HOXD10 mRNA expression levels in the cancer tissue of individuals with lymph node were significantly higher than patients without lymph node(9.01±1.22) vs(7.81±2.15),P =0.02). There were positive correlation relationships between the expressions of HOTTIP and its downstream gene HOXA13 mRNA in cancer tissue(r = 0.78,P < 0.01) and adjacent normal tissue(r = 0.70,P < 0.01);the HOTAIR and its downstream HOXD10 gene mRNA in adjacent normal tissue were positively related(r = 0.37,P =0.01),but not correlated in cancer tissues(r = 0.12,P = 0.47). Conclusions The regulation between HOTTIP and HOXA13 is normal in lung cancer. The expression of HOTAIR decreases in cancer tissues,and HOTAIR may lose the normal regulation of downstream genes of HOXD10.
引文
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[2]PONTING C P,OLIVER P L,REIK W.Evolution and functions of long noncoding RNAs[J].Cell,2009,136(4):629-641.
[3]王俊青,张彦洁,任建敏,等.长链非编码RNA生物学功能及其意义研究进展[J].生命科学,2012,5(6):543-548.
[4]RINN J L,KERTESZ M,WANG J K,et al.Functional demarcation of active and silent chromatin domains in human HOX loci by non-coding RNAs[J].Cell,2007,129(7):1 311.
[5]WANG K C,YANG Y W,LIU B,et al.A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression[J].Nature,2011,472(7 341):120-124.
[6]KIM K,JUTOORU I,CHADALAPAKA G,et al.HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer[J].Oncogene,2012,21(193).1-10.
[7]GUPTA R A,SHAH N,WANG K C,et al.Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis[J].Nature,2010,464(7 291):1 071-1 076.
[8]KOGO R,SHIMAMURA T,MIMORI K,et al.Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers[J].Cancer research,2011,71(20):6 320-6 326.
[9]YANG Z,ZHOU L,WU L M,et al.Over expression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation[J].Annals of surgical oncology,2011,18(5):1 243-1 250.
[10]WANG L,CHEN S,XUE M,et al.Homeobox D10 gene,a candidate tumor suppressor,is down regulated through promoter hypermethylation and associated with gastric carcinogenesis[J].Mol Med,2012,9(18):389-400.