Increased expression of antisense lncRNA SPINT1-AS1 predicts a poor prognosis in colorectal cancer and is negatively correlated with its sense transcript

被引：42
作者：
Li, Chen [1 ]
Li, Wei [2 ]
Zhang, Yanli [3 ]
Zhang, Xin [2 ]
Liu, Tong [1 ]
Zhang, Yi [2 ]
Yang, Yongmei [2 ]
Wang, Lili [2 ]
Pan, Hongwei [2 ]
Ji, Jian [2 ]
Wang, Chuanxin [1 ]
机构：
[1] Shandong Univ, Hosp 2, Dept Clin Lab, 247 Beiyuan St, Jinan 250033, Shandong, Peoples R China
[2] Shandong Univ, Dept Clin Lab, Qilu Hosp, Jinan 250012, Shandong, Peoples R China
[3] Shandong Prov Third Hosp, Dept Clin Lab, Jinan 250031, Shandong, Peoples R China
来源：
ONCOTARGETS AND THERAPY | 2018年 / 11卷
基金：
中国国家自然科学基金;
关键词：
colorectal cancer; natural antisense transcripts; SPINT1-AS1; SPINT1; mRNA; prognosis; HEPATOCYTE GROWTH-FACTOR; FACTOR ACTIVATOR INHIBITOR; RNA; TYPE-1; HAI-1; MATRIPTASE; PROTEIN; ROLES; CELLS; FORM;
D O I：
10.2147/OTT.S163883
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
Purpose: Colorectal cancer (CRC) is a leading cause of cancer-associated mortality worldwide. Natural antisense transcripts (NATs) are pervasively expressed in human genome and have been confirmed to contribute to cancer progression. In our study, we aimed to investigate the expression and clinical pertinence of serine peptidase inhibitor, Kunitz type 1 antisense RNA1 (SPINT1-AS1) in CRC. Materials and methods: The expression levels of SPINT1-AS1 and the corresponding sense transcript SPINT1 mRNA were analyzed in 150 pairs of CRC tissues and adjacent normal (AN) tissues, along with 45 pairs of preoperative and postoperative serum exosome samples by the strand-specific real-time quantitative polymerise chain reaction. Results: Compared with AN tissues, the expression of SPINT1-AS1 was increased (P<0.001, 3.771 vs 0.980) in CRC tissues, while SPINT1 mRNA expression was decreased in CRC (P<0.001, 0.927 vs 1.165), and there was an obviously negative correlation between SPINT1-AS1 expression and its sense transcript (r=-0.701, P<0.001). SPINT1-AS1 yielded an area under the receiver operating characteristic curve value of 0.865 (95% confidence interval, 0.821-0.902) for discriminating CRC tissues from AN tissues. Moreover, high SPINT1-AS1 expression was correlated with regional lymph node metastasis (P<0.001), distant metastasis (P<0.001), and shorter relapse-free survival (RFS) time (P<0.001), and Cox regression analysis indicated that SPINT1-ASI was an independent prognostic factor for RFS. Meanwhile, significant reduction of SPINT1-AS1 expression level (P=0.001) was observed in CRC serum exosomes after surgical resection. Conclusion: SPINT1-AS1 is upregulated in CRC tissues and plays an essential role in CRC progression and prognosis. Thereby, SPINT1-AS1 may serve as a candidate prognostic biomarker and molecular therapy target for CRC.
引用
收藏
页码：3969 / 3978
页数：10
相关论文
共 39 条
[1]   The landscape of antisense gene expression in human cancers [J].
Balbin, O. Alejandro ;
Malik, Rohit ;
Dhanasekaran, Saravana M. ;
Prensner, John R. ;
Cao, Xuhong ;
Wu, Yi-Mi ;
Robinson, Dan ;
Wang, Rui ;
Chen, Guoan ;
Beer, David G. ;
Nesvizhskii, Alexey I. ;
Chinnaiyan, Arul M. .
GENOME RESEARCH, 2015, 25 (07) :1068-1079
[2]   Over 20% of human transcripts might form sense-antisense pairs [J].
Chen, JJ ;
Sun, M ;
Kent, WJ ;
Huang, XQ ;
Xie, HQ ;
Wang, WQ ;
Zhou, GL ;
Shi, RZ ;
Rowley, JD .
NUCLEIC ACIDS RESEARCH, 2004, 32 (16) :4812-4820
[3]   Expression of a large LINE-1-driven antisense RNA is linked to epigenetic silencing of the metastasis suppressor gene TFPI-2 in cancer [J].
Cruickshanks, Hazel A. ;
Vafadar-Isfahani, Natasha ;
Dunican, Donncha S. ;
Lee, Andy ;
Sproul, Duncan ;
Lund, Jonathan N. ;
Meehan, Richard R. ;
Tufarelli, Cristina .
NUCLEIC ACIDS RESEARCH, 2013, 41 (14) :6857-6869
[4]   Regulatory roles of natural antisense transcripts [J].
Faghihi, Mohammad Ali ;
Wahlestedt, Claes .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2009, 10 (09) :637-643
[5]   Long non-coding RNAs: new players in cell differentiation and development [J].
Fatica, Alessandro ;
Bozzoni, Irene .
NATURE REVIEWS GENETICS, 2014, 15 (01) :7-21
[6]   PROCESSING OF HEPATOCYTE GROWTH-FACTOR TO THE HETERODIMERIC FORM IS REQUIRED FOR BIOLOGICAL-ACTIVITY [J].
GAK, E ;
TAYLOR, WG ;
CHAN, AML ;
RUBIN, JS .
FEBS LETTERS, 1992, 311 (01) :17-21
[7]   A Primary Role for the Tsix lncRNA in Maintaining Random X-Chromosome Inactivation [J].
Gayen, Srimonta ;
Maclary, Emily ;
Buttigieg, Emily ;
Hinten, Michael ;
Kalantry, Sundeep .
CELL REPORTS, 2015, 11 (08) :1251-1265
[8]   Association Between Concentrations of Hemoglobin Determined by Fecal Immunochemical Tests and Long-term Development of Advanced Colorectal Neoplasia [J].
Grobbee, Esmee J. ;
Schreuders, Eline H. ;
Hansen, Bettina E. ;
Bruno, Marco J. ;
Lansdorp-Vogelaar, Iris ;
Spaander, Manon C. W. ;
Kuipers, Ernst J. .
GASTROENTEROLOGY, 2017, 153 (05) :1251-+
[9]   Hepatocyte Growth Factor Activator Inhibitor Type 1 Is a Suppressor of Intestinal Tumorigenesis [J].
Hoshiko, Shinri ;
Kawaguchi, Makiko ;
Fukushima, Tsuyoshi ;
Haruyama, Yukihiro ;
Yorita, Kenji ;
Tanaka, Hiroyuki ;
Seiki, Motoharu ;
Inatsu, Haruhiko ;
Kitamura, Kazuo ;
Kataoka, Hiroaki .
CANCER RESEARCH, 2013, 73 (08) :2659-2670
[10]   Long non-coding antisense RNA KRT7-AS is activated in gastric cancers and supports cancer cell progression by increasing KRT7 expression [J].
Huang, B. ;
Song, J. H. ;
Cheng, Y. ;
Abraham, J. M. ;
Ibrahim, S. ;
Sun, Z. ;
Ke, X. ;
Meltzer, S. J. .
ONCOGENE, 2016, 35 (37) :4927-4936
1234