长链非编码RNA HULC与消化系统肿瘤的相关性研究及作用机制
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摘要
随着全基因组测序技术的快速发展,越来越多的长链非编码RNA(long noncoding RNA, lncRNA)分子被发现,逐渐成为新的研究热点。LncRNA HULC(highly up-regulated in liver cancer)是一种在肝癌中呈异常上调表达的长链非编码RNA,并参与调控了肝癌细胞增殖、抗凋亡、侵袭及上皮间质化等诸多肿瘤恶性生物学行为。随着研究的不断深入,发现HULC于其他消化系统肿瘤(胃癌、胰腺癌、结肠癌等)中同样呈现上调表达,可通过不同作用机制调控肿瘤的发生发展,并有望成为新型肿瘤诊断标志物和精准分子治疗的靶点。本文就近年来LncRNA HULC与消化系统肿瘤的相关性研究及其作用机制进行综述。
With the rapid development of the whole genome sequencing technology, a growing number of long non-coding RNAs have been discovered and gradually become new research highlights. LncRNA HULC(highly up-regulated in liver cancer)is one of non-coding RNAs that abnormally upregulated in hepatocellular carcinoma while involved in the regulation of various malignant biological behaviors including tumor cell proliferation, anti-apoptosis, invasion and epithelial-mesenchymal transition. With the deepening of the study, HULC was found dysregulated in various digestive neoplasms, including gastric cancer, pancreatic cancer,colorectal cancer and many others, and different molecule mechanisms have been demonstrated to be involved in tumor progression. To sum up, it is expected to become the new biomarker and accurate molecular target of therapy. This review briefly presented the relevance between HULC and digestive neoplasms together with the underlying regulatory mechanisms.
With the rapid development of the whole genome sequencing technology, a growing number of long non-coding RNAs have been discovered and gradually become new research highlights. LncRNA HULC(highly up-regulated in liver cancer)is one of non-coding RNAs that abnormally upregulated in hepatocellular carcinoma while involved in the regulation of various malignant biological behaviors including tumor cell proliferation, anti-apoptosis, invasion and epithelial-mesenchymal transition. With the deepening of the study, HULC was found dysregulated in various digestive neoplasms, including gastric cancer, pancreatic cancer,colorectal cancer and many others, and different molecule mechanisms have been demonstrated to be involved in tumor progression. To sum up, it is expected to become the new biomarker and accurate molecular target of therapy. This review briefly presented the relevance between HULC and digestive neoplasms together with the underlying regulatory mechanisms.
引文
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[7] Mendell JT. Targeting a Long Noncoding RNA in Breast Cancer[J]. NEngl J Med, 2016, 374(23):2287-2289
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[11] Atianand MK, Hu W, Satpathy AT, et al. A Long Noncoding RNAlincRNA-EPS Acts as a Transcriptional Brake to RestrainInflammation[J]. Cell, 2016, 165(7):1672-1685
[12] White NM, Zhao SG, Zhang J, et al. Multi-institutional AnalysisShows that Low PCAT-14 Expression Associates with PoorOutcomes in Prostate Cancer[J]. Eur Urol, 2017, 71(2):257-266
[13] Li C, Wang S, Xing Z, et al. A ROR1-HER3-lncRNA signalling axismodulates the Hippo-YAP pathway to regulate bone metastasis[J].Nat Cell Biol, 2017, 19(2):106-119
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[15] Zhang A, Xu M, Mo YY. Role of the lncRNA-p53 regulatorynetwork in cancer[J]. J Mol Cell Biol, 2014, 6(3):181-191
[16] Yang Z, Lu Y, Xu Q, et al. HULC and H19 Played Different Roles inOverall and Disease-Free Survival from Hepatocellular Carcinomaafter Curative Hepatectomy:A Preliminary Analysis from GeneExpression Omnibus[J]. Dis Markers, 2015, 2015:191029
[17] Li J, Wang X, Tang J, et al. HULC and Linc00152 Act as NovelBiomarkers in Predicting Diagnosis of Hepatocellular Carcinoma[J].Cell Physiol Biochem, 2015, 37(2):687-696
[18] Wu M, Lin Z, Li X, et al. HULC cooperates with MALAT1 toaggravate liver cancer stem cells growth through telomererepeat-binding factor 2[J]. Sci Rep, 2016, 6:36045
[19] Cloutier SC, Wang S, Ma WK, et al. Regulated Formation oflncRNA-DNA Hybrids Enables Faster Transcriptional Induction andEnvironmental Adaptation[J]. Mol Cell, 2016, 61(3):393-404
[20] Cabili MN, Trapnell C, Goff L, et al. Integrative annotation of humanlarge intergenic noncoding RNAs reveals global properties andspecific subclasses[J]. Genes Dev, 2011, 25(18):1915-1927
[21] Younger ST, Rinn JL.'Lnc'-ing enhancers to MYC regulation[J]. CellRes, 2014, 24(6):643-644
[22] Li W, Kang Y. A new Lnc in metastasis:long noncoding RNAmediates the prometastatic functions of TGF-β[J]. Cancer cell, 2014,25(5):557-559
[23] Jemal A, Bray F, Center MM, et al. Global cancer statistics[J]. CACancer J Clin, 2011, 61(2):69-90
[24] Gao T, He B, Pan Y, et al. Long non-coding RNA 91H contributes tothe occurrence and progression of esophageal squamous cellcarcinoma by inhibiting IGF2 expression[J]. Mol Carcinog, 2015, 54(5):359-367
[25] Lv XB, Lian GY, Wang HR, et al. Long noncoding RNA HOTAIR isa prognostic marker for esophageal squamous cell carcinomaprogression and survival[J]. PloS one, 2013, 8(5):e63516
[26] Xu Y, Wang J, Qiu M, et al. Upregulation of the long noncodingRNA TUG1 promotes proliferation and migration of esophagealsquamous cell carcinoma[J]. Tumour Biol, 2015, 36(3):1643-1651
[27] Kang M, Sang Y, Gu H, et al. Long noncoding RNAs POLR2Ers3787016 C/T and HULC rs7763881 A/C polymorphisms areassociated with decreased risk of esophageal cancer[J]. Tumour Biol,2015, 36(8):6401-6408
[28] Zhao Y, Guo Q, Chen J, et al. Role of long non-coding RNA HULCin cell proliferation, apoptosis and tumor metastasis of gastric cancer:a clinical and in vitro investigation[J]. Oncol Rep, 2014, 31(1):358-364
[29] Jin C, Shi W, Wang F, et al. Long non-coding RNA HULC as a novelserum biomarker for diagnosis and prognosis prediction of gastriccancer[J]. Oncotarget, 2016, 7(32):51763-51772
[30] Hwang S, Ko GY, Kim MH, et al. Preoperative Left Portal VeinEmbolization for Left Liver Resection in High-Risk HepatobiliaryMalignancy Patients[J]. World J Surg, 2016, 40:2758-2765
[31] H覿mmerle M, Gutschner T, Uckelmann H, et al. Posttranscriptionaldestabilization of the liver-specific long noncoding RNA HULC bythe IGF2 mRNA-binding protein 1(IGF2BP1)[J]. Hepatology, 2013,58(5):1703-1712
[32] Wan D, Shen S, Fu S, et al. miR-203 suppresses the proliferation andmetastasis of hepatocellular carcinoma by targeting oncogeneADAM9 and oncogenic long non-coding RNA HULC[J]. AnticancerAgents Med Chem, 2016, 16(4):414-423
[33] Yang X, Xie X, Xiao YF, et al. The emergence of long non-codingRNAs in the tumorigenesis of hepatocellular carcinoma[J]. CancerLett, 2015, 360(2):119-124
[34] Xie H, Ma H, Zhou D. Plasma HULC as a promising novel biomarkerfor the detection of hepatocellular carcinoma[J]. Biomed Res Int,2013, 2013:136106
[35] Wang J, Liu X, Wu H, et al. CREB up-regulates long non-codingRNA, HULC expression through interaction with microRNA-372 inliver cancer[J]. Nucleic Acids Res, 2010, 38(16):5366-5383
[36] Du Y, Kong G, You X, et al. Elevation of highly up-regulated in livercancer(HULC)by hepatitis B virus X protein promotes hepatoma cellproliferation via down-regulating p18[J]. J Biol Chem, 2012, 287(31):26302-26311
[37] Li SP, Xu HX, Yu Y, et al. LncRNA HULC enhances epithelial-mesenchymal transition to promote tumorigenesis and metastasis ofhepatocellular carcinoma via the miR-200a-3p/ZEB1 signalingpathway[J]. Oncotarget, 2016, 7(27):42431-42446
[38] Cui M, Xiao Z, Wang Y, et al. Long noncoding RNA HULCmodulates abnormal lipid metabolism in hepatoma cells through anmiR-9-mediated RXRA signaling pathway[J]. Cancer Res, 2015, 75(5):846-857
[39] Yang XJ, Huang CQ, Peng CW, et al. Long noncoding RNA HULCpromotes colorectal carcinoma progression through epigeneticallyrepressing NKD2 expression[J]. Gene, 2016, 592(1):172-178
[40] Matouk IJ, Abbasi I, Hochberg A, et al. Highly upregulated in livercancer noncoding RNA is overexpressed in hepatic colorectalmetastasis[J]. Eur J Gastroenterol Hepatol, 2009, 21(6):688-692
[41] Peng W, Gao W, Feng J. Long noncoding RNA HULC is a novelbiomarker of poor prognosis in patients with pancreatic cancer[J].Med Oncol, 2014, 31(12):346
[42] Wang WT, Ye H, Wei PP, et al. LncRNAs H19 and HULC, activatedby oxidative stress, promote cell migration and invasion incholangiocarcinoma through a ce RNA manner[J]. J Hematol Oncol,2016, 9(1):117
[43] Liu R, Zeng Y, Zhou CF, et al. Long noncoding RNA expressionsignature to predict platinum-based chemotherapeutic sensitivity ofovarian cancer patients[J]. Sci Rep, 2017, 7(1):18
[44] Shukla S, Evans JR, Malik R, et al. Development of a RNA-SeqBased Prognostic Signature in Lung Adenocarcinoma[J]. J NatlCancer Inst, 2017, 109(1)
[45] Beaver LM, Kuintzle R, Buchanan A, et al. Long noncoding RNAsand sulforaphane:a target for chemoprevention and suppression ofprostate cancer[J]. J Nutr Biochem, 2017, 42:72-83
[46] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2):115-132
[2] Derrien T, Johnson R, Bussotti G, et al. The GENCODE v7 catalog ofhuman long noncoding RNAs:analysis of their gene structure,evolution, and expression[J]. Genome Res, 2012, 22(9):1775-1789
[3] Wang KC, Chang HY. Molecular mechanisms of long noncodingRNAs[J]. Mol Cell, 2011, 43(6):904-914
[4] Costa FF. Non-coding RNAs:Meet thy masters[J]. BioEssays, 2010,32(7):599-608
[5]施伟,赵健,宋晓峰,等. LincRNA的研究进展[J].现代生物医学进展, 2016, 16(09):1762-1765+1714Shi Wei, Zhao Jian, Song Xiao-feng, et al. Research Progress ofLincRNA[J]. Progress in Modern Biomedicine, 2016, 16(09):1762-1765+1714
[6] Leucci E, Vendramin R, Spinazzi M, et al. Melanoma addiction to thelong non-coding RNA SAMMSON[J]. Nature, 2016, 531(7595):518-522
[7] Mendell JT. Targeting a Long Noncoding RNA in Breast Cancer[J]. NEngl J Med, 2016, 374(23):2287-2289
[8] Chen LL, Carmichael GG. Decoding the function of nuclear longnon-coding RNAs[J]. Curr Opin Cell Biol, 2010, 22(3):357-364
[9] Gutschner T, Diederichs S. The hallmarks of cancer:a longnon-coding RNA point of view[J]. RNA Biol, 2012, 9:703-719
[10] Fujimoto A, Furuta M, Totoki Y, et al. Whole-genome mutationallandscape and characterization of noncoding and structural mutationsin liver cancer[J]. Nat Genet, 2016, 48(5):500-509
[11] Atianand MK, Hu W, Satpathy AT, et al. A Long Noncoding RNAlincRNA-EPS Acts as a Transcriptional Brake to RestrainInflammation[J]. Cell, 2016, 165(7):1672-1685
[12] White NM, Zhao SG, Zhang J, et al. Multi-institutional AnalysisShows that Low PCAT-14 Expression Associates with PoorOutcomes in Prostate Cancer[J]. Eur Urol, 2017, 71(2):257-266
[13] Li C, Wang S, Xing Z, et al. A ROR1-HER3-lncRNA signalling axismodulates the Hippo-YAP pathway to regulate bone metastasis[J].Nat Cell Biol, 2017, 19(2):106-119
[14] Panzitt K, Tschernatsch MM, Guelly C, et al. Characterization ofHULC, a novel gene with striking up-regulation in hepatocellularcarcinoma, as noncoding RNA[J]. Gastroenterology, 2007, 132(1):330-342
[15] Zhang A, Xu M, Mo YY. Role of the lncRNA-p53 regulatorynetwork in cancer[J]. J Mol Cell Biol, 2014, 6(3):181-191
[16] Yang Z, Lu Y, Xu Q, et al. HULC and H19 Played Different Roles inOverall and Disease-Free Survival from Hepatocellular Carcinomaafter Curative Hepatectomy:A Preliminary Analysis from GeneExpression Omnibus[J]. Dis Markers, 2015, 2015:191029
[17] Li J, Wang X, Tang J, et al. HULC and Linc00152 Act as NovelBiomarkers in Predicting Diagnosis of Hepatocellular Carcinoma[J].Cell Physiol Biochem, 2015, 37(2):687-696
[18] Wu M, Lin Z, Li X, et al. HULC cooperates with MALAT1 toaggravate liver cancer stem cells growth through telomererepeat-binding factor 2[J]. Sci Rep, 2016, 6:36045
[19] Cloutier SC, Wang S, Ma WK, et al. Regulated Formation oflncRNA-DNA Hybrids Enables Faster Transcriptional Induction andEnvironmental Adaptation[J]. Mol Cell, 2016, 61(3):393-404
[20] Cabili MN, Trapnell C, Goff L, et al. Integrative annotation of humanlarge intergenic noncoding RNAs reveals global properties andspecific subclasses[J]. Genes Dev, 2011, 25(18):1915-1927
[21] Younger ST, Rinn JL.'Lnc'-ing enhancers to MYC regulation[J]. CellRes, 2014, 24(6):643-644
[22] Li W, Kang Y. A new Lnc in metastasis:long noncoding RNAmediates the prometastatic functions of TGF-β[J]. Cancer cell, 2014,25(5):557-559
[23] Jemal A, Bray F, Center MM, et al. Global cancer statistics[J]. CACancer J Clin, 2011, 61(2):69-90
[24] Gao T, He B, Pan Y, et al. Long non-coding RNA 91H contributes tothe occurrence and progression of esophageal squamous cellcarcinoma by inhibiting IGF2 expression[J]. Mol Carcinog, 2015, 54(5):359-367
[25] Lv XB, Lian GY, Wang HR, et al. Long noncoding RNA HOTAIR isa prognostic marker for esophageal squamous cell carcinomaprogression and survival[J]. PloS one, 2013, 8(5):e63516
[26] Xu Y, Wang J, Qiu M, et al. Upregulation of the long noncodingRNA TUG1 promotes proliferation and migration of esophagealsquamous cell carcinoma[J]. Tumour Biol, 2015, 36(3):1643-1651
[27] Kang M, Sang Y, Gu H, et al. Long noncoding RNAs POLR2Ers3787016 C/T and HULC rs7763881 A/C polymorphisms areassociated with decreased risk of esophageal cancer[J]. Tumour Biol,2015, 36(8):6401-6408
[28] Zhao Y, Guo Q, Chen J, et al. Role of long non-coding RNA HULCin cell proliferation, apoptosis and tumor metastasis of gastric cancer:a clinical and in vitro investigation[J]. Oncol Rep, 2014, 31(1):358-364
[29] Jin C, Shi W, Wang F, et al. Long non-coding RNA HULC as a novelserum biomarker for diagnosis and prognosis prediction of gastriccancer[J]. Oncotarget, 2016, 7(32):51763-51772
[30] Hwang S, Ko GY, Kim MH, et al. Preoperative Left Portal VeinEmbolization for Left Liver Resection in High-Risk HepatobiliaryMalignancy Patients[J]. World J Surg, 2016, 40:2758-2765
[31] H覿mmerle M, Gutschner T, Uckelmann H, et al. Posttranscriptionaldestabilization of the liver-specific long noncoding RNA HULC bythe IGF2 mRNA-binding protein 1(IGF2BP1)[J]. Hepatology, 2013,58(5):1703-1712
[32] Wan D, Shen S, Fu S, et al. miR-203 suppresses the proliferation andmetastasis of hepatocellular carcinoma by targeting oncogeneADAM9 and oncogenic long non-coding RNA HULC[J]. AnticancerAgents Med Chem, 2016, 16(4):414-423
[33] Yang X, Xie X, Xiao YF, et al. The emergence of long non-codingRNAs in the tumorigenesis of hepatocellular carcinoma[J]. CancerLett, 2015, 360(2):119-124
[34] Xie H, Ma H, Zhou D. Plasma HULC as a promising novel biomarkerfor the detection of hepatocellular carcinoma[J]. Biomed Res Int,2013, 2013:136106
[35] Wang J, Liu X, Wu H, et al. CREB up-regulates long non-codingRNA, HULC expression through interaction with microRNA-372 inliver cancer[J]. Nucleic Acids Res, 2010, 38(16):5366-5383
[36] Du Y, Kong G, You X, et al. Elevation of highly up-regulated in livercancer(HULC)by hepatitis B virus X protein promotes hepatoma cellproliferation via down-regulating p18[J]. J Biol Chem, 2012, 287(31):26302-26311
[37] Li SP, Xu HX, Yu Y, et al. LncRNA HULC enhances epithelial-mesenchymal transition to promote tumorigenesis and metastasis ofhepatocellular carcinoma via the miR-200a-3p/ZEB1 signalingpathway[J]. Oncotarget, 2016, 7(27):42431-42446
[38] Cui M, Xiao Z, Wang Y, et al. Long noncoding RNA HULCmodulates abnormal lipid metabolism in hepatoma cells through anmiR-9-mediated RXRA signaling pathway[J]. Cancer Res, 2015, 75(5):846-857
[39] Yang XJ, Huang CQ, Peng CW, et al. Long noncoding RNA HULCpromotes colorectal carcinoma progression through epigeneticallyrepressing NKD2 expression[J]. Gene, 2016, 592(1):172-178
[40] Matouk IJ, Abbasi I, Hochberg A, et al. Highly upregulated in livercancer noncoding RNA is overexpressed in hepatic colorectalmetastasis[J]. Eur J Gastroenterol Hepatol, 2009, 21(6):688-692
[41] Peng W, Gao W, Feng J. Long noncoding RNA HULC is a novelbiomarker of poor prognosis in patients with pancreatic cancer[J].Med Oncol, 2014, 31(12):346
[42] Wang WT, Ye H, Wei PP, et al. LncRNAs H19 and HULC, activatedby oxidative stress, promote cell migration and invasion incholangiocarcinoma through a ce RNA manner[J]. J Hematol Oncol,2016, 9(1):117
[43] Liu R, Zeng Y, Zhou CF, et al. Long noncoding RNA expressionsignature to predict platinum-based chemotherapeutic sensitivity ofovarian cancer patients[J]. Sci Rep, 2017, 7(1):18
[44] Shukla S, Evans JR, Malik R, et al. Development of a RNA-SeqBased Prognostic Signature in Lung Adenocarcinoma[J]. J NatlCancer Inst, 2017, 109(1)
[45] Beaver LM, Kuintzle R, Buchanan A, et al. Long noncoding RNAsand sulforaphane:a target for chemoprevention and suppression ofprostate cancer[J]. J Nutr Biochem, 2017, 42:72-83
[46] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2):115-132
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