TY - JOUR
T1 - ZFR promotes cell proliferation and tumor development in colorectal and liver cancers
AU - Long, Yanrong
AU - Marian, Teresa A.
AU - Wei, Zhubo
N1 - Funding Information:
We thank other research groups in Houston Methodist Cancer Center for equipment and technical supports. We also thank the mouse facility at Houston Methodist Research Institute for high-quality animal care. This work was supported by the faculty start-up fund to Z.W. from Houston Methodist. Z.W. designed the research and wrote the manuscript. Y.L. and H.L. performed the experiments. We declare no conflicts of interests, financial or otherwise.
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/6/11
Y1 - 2019/6/11
N2 - Colorectal cancer (CRC) and liver cancer are the second and fourth leading causes of cancer-related deaths in the whole world, respectively, and each year over 1.6 million people die from these diseases. To identify driver genes in CRC and liver cancer, we have performed Sleeping Beauty transposon mutagenesis screens in mouse models. Zinc finger RNA binding protein, ZFR, was one of the novel candidate cancer genes identified in these forward genetic screens. Consistent with this discovery, a pan-cancer analysis of sequencing results of thousands of human cancer genomes demonstrated that ZFR is a potential potent oncogene. In this study, we aimed to investigate ZFR's roles in both types of cancer and found that overexpression of ZFR in CRC and liver cancer cells led to accelerated tumor development. Consistently, knockdown of ZFR resulted in significantly decelerated tumor development. ZFR overexpression also promoted tumor development of immortalized mouse liver cells. ZFR overexpression and shRNA knockdown led to accelerated and decelerated cell proliferation, respectively, indicating that ZFR promotes tumor development mainly by regulating cell proliferation. To identify ZFR's targets in transcription, we performed whole transcriptome sequencing using ZFR small interfering RNAs in a primary human colon cell line. All potential target genes were validated by real time PCR. FAM49B was a tumor suppressor candidate for ZFR targets. When we knocked down the expression of FAM49B in CRC and liver cancer cells, we observed significantly accelerated cell proliferation, consistent with the results with ZFR overexpression. The results presented here demonstrate the oncogenic role of ZFR in both CRC and liver cancer, providing a potential drug target for both cancers' treatment. We also identified ZFR's potential transcriptional targets, and further investigations on those targets, especially FAM49B, will help us understand more about the important role of ZFR in digestive system cancers.
AB - Colorectal cancer (CRC) and liver cancer are the second and fourth leading causes of cancer-related deaths in the whole world, respectively, and each year over 1.6 million people die from these diseases. To identify driver genes in CRC and liver cancer, we have performed Sleeping Beauty transposon mutagenesis screens in mouse models. Zinc finger RNA binding protein, ZFR, was one of the novel candidate cancer genes identified in these forward genetic screens. Consistent with this discovery, a pan-cancer analysis of sequencing results of thousands of human cancer genomes demonstrated that ZFR is a potential potent oncogene. In this study, we aimed to investigate ZFR's roles in both types of cancer and found that overexpression of ZFR in CRC and liver cancer cells led to accelerated tumor development. Consistently, knockdown of ZFR resulted in significantly decelerated tumor development. ZFR overexpression also promoted tumor development of immortalized mouse liver cells. ZFR overexpression and shRNA knockdown led to accelerated and decelerated cell proliferation, respectively, indicating that ZFR promotes tumor development mainly by regulating cell proliferation. To identify ZFR's targets in transcription, we performed whole transcriptome sequencing using ZFR small interfering RNAs in a primary human colon cell line. All potential target genes were validated by real time PCR. FAM49B was a tumor suppressor candidate for ZFR targets. When we knocked down the expression of FAM49B in CRC and liver cancer cells, we observed significantly accelerated cell proliferation, consistent with the results with ZFR overexpression. The results presented here demonstrate the oncogenic role of ZFR in both CRC and liver cancer, providing a potential drug target for both cancers' treatment. We also identified ZFR's potential transcriptional targets, and further investigations on those targets, especially FAM49B, will help us understand more about the important role of ZFR in digestive system cancers.
KW - Colorectal cancer
KW - FAM49B
KW - Liver cancer
KW - Oncogene
KW - Proliferation
KW - ZFR
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U2 - 10.1016/j.bbrc.2019.04.103
DO - 10.1016/j.bbrc.2019.04.103
M3 - Article
C2 - 31010678
AN - SCOPUS:85064426880
SN - 0006-291X
VL - 513
SP - 1027
EP - 1034
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -