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学科主题: 临床医学
题名:
Shortening of the 3 ′ untranslated region: an important mechanism leading to overexpression of HMGA2 in serous ovarian cancer
作者: He Xiangjun1; Yang Jing1; Zhang Qi1; Cui Heng2; Zhang Yujun1
关键词: HMGA2 overexpression ; 3 &prime ; UTR shortening ; microRNA regulation ; serous ovarian cancer
刊名: CHINESE MEDICAL JOURNAL
发表日期: 2014-02-05
DOI: 10.3760/cma.j.issn.0366-6999.20130843
卷: 127, 期:3, 页:494-499
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Medicine, General & Internal
研究领域[WOS]: General & Internal Medicine
关键词[WOS]: ALTERNATIVE CLEAVAGE ; MESSENGER-RNAS ; LET-7 ; POLYADENYLATION ; CELLS ; EXPRESSION ; CARCINOMA
英文摘要:

Background Oncofetal protein high-mobility-group AT-hook protein 2 (HMGA2) is reactivated in serous ovarian cancer (SOC) and its overexpression correlates with poor prognosis. To explore the mechanism, we investigated whether HMGA2 could avoid microRNA regulation due to gene truncation or 3′ UTR shortening by alternative polyadenylation.

Methods Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate the abundance of different regions of HMGA2 mRNA in 46 SOC samples. Rapid amplification of cDNA 3′ ends (3′ RACE) and Southern blotting were used to confirm the shortening of 3′ untranslated region (UTR). 5′ RACE and Southern blotting were used to prove the mRNA decay.

Results No significant difference in the ratio of the stable coding region to the fragile region was observed between SOC and control normal fallopian tubes, indicating that the HMGA2 gene is not truncated in SOC. Varying degrees of 3′ UTR shortening in SOC samples were observed by comparing the abundance of the proximal region and distal region of the HMGA2 3′ UTR. The ratio of the proximal to the distal region of the 3′ UTR correlated significantly with expression of the HMGA2 coding region in SOC (r=0.579, P<0.01). Moreover, although the abundance of the HMGA2 coding region varied, all samples, including the very low expressed samples, exhibit relatively high levels of the proximal 3′ UTR region, suggesting a dynamic decay of HMGA2 mRNA from the 5′ end. The shortening of 3′ UTR and the decay from the 5′ end were confirmed by 3′ RACE, 5′ RACE and subsequent Southern blotting.

Conclusion Heterogeneous 3′ UTR lengths render HMGA2 susceptible to different levels of negative regulation by microRNAs, which represents an important mechanism of HMGA2 reactivation in SOC.

语种: 英语
所属项目编号: RDB 2011-23
项目资助者: Peking University People&prime ; s Hospital Research and Development Fund
WOS记录号: WOS:000333498400017
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/49894
Appears in Collections:北京大学第二临床医学院_临床分子生物学研究所_期刊论文

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作者单位: 1.Peking Univ, Peoples Hosp, Inst Clin Mol Biol, Beijing 100044, Peoples R China
2.Peking Univ, Peoples Hosp, Gynecol Oncol Ctr, Beijing 100044, Peoples R China

Recommended Citation:
He Xiangjun,Yang Jing,Zhang Qi,et al. Shortening of the 3 ′ untranslated region: an important mechanism leading to overexpression of HMGA2 in serous ovarian cancer[J]. CHINESE MEDICAL JOURNAL,2014,127(3):494-499.
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