Microarray Analysis of Long Non-coding RNA Expression Profile Associated with 5-Fluorouracil-Based Chemoradiation Resistance in Colorectal Cancer Cells.
BACKGROUND
Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study.


METHODS
A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines.


RESULTS
In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak- STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes.


CONCLUSIONS
Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.
Department of Radiation Oncology, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, China E-mail : wenhuili64@163.com.
Wei
W
Xiong
Yong-Xin
YX
Jiang
Yi-Qin
YQ
Ai
Shan
S
Liu
Xing-Rao
XR
Wu
Jian-Guo
JG
Cui
Ji-Yong
JY
Qin
Yan
Y
Liu
Yao-Xiong
YX
Xia
Yun-He
YH
Ju
Wen-Jie
WJ
He
Yong
Y
Wang
Yun-Fen
YF
Li
Yu
Y
Hou
Li
L
Wang
Wen-Hui
WH
Li
D000970:Antineoplastic Agents; D059248:Chemoradiotherapy; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000628:therapy; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005472:Fluorouracil; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D053612:Janus Kinases / Q000235:genetics; D046228:Microarray Analysis; D016328:NF-kappa B / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D011836:Radiation Tolerance / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D050791:STAT Transcription Factors / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
D000970:Antineoplastic Agents; D016328:NF-kappa B; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D050791:STAT Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D053612:Janus Kinases; D051057:Proto-Oncogene Proteins c-akt; D005472:Fluorouracil