Abstract
Recently, a novel class of transcripts, long noncoding RNAs (lncRNAs), is being identified at a rapid pace. These RNAs have critical roles in diverse biological processes, including tumorigenesis. One of them, BLACAT1, a cancer-associated long noncoding RNA, exerts regulatory functions in various biological processes in cancer cells, however, the role of BLACAT1 in colon cancer remains unclear. Our experiments showed that increased BLACAT1 was an independent unfavorable prognostic indicator for colorectal cancer, and revealed that BLACAT1 knockdown significantly repressed proliferation, both in vitro and in vivo. Mechanistic investigations demonstrated that BLACAT1 had a key role in G1/G0 arrest, and showed that BLACAT1 can repress p15 expression by binding to EZH2, thus contributing to the regulation of CRC cell cycle and proliferation. Our results suggest that BLACAT1, as a cell cycle regulator, may serve as a potential target for colon cancer prevention and treatment in human CRC.
Highlights
Colorectal cancer is a common cause of cancer death in the world due to late tumor presentation and rapid progression, with about 13 million new cancer cases and 694000 cancer deaths in 2012 worldwide.[1,2] China is one of the countries with high incidence of CRC, in which CRC ranks third among all cancer sites in cancer incidence and fifth in cancer mortality.[3]
HOTAIR, functioning as an oncogene, that can be used to predict the prognosis in non-small cell lung cancer (NSCLC) patients and determine whether or not patient can benefit from chemotherapy.[16,17]
We explored the function of BLACAT1 by using in vitro and in vivo assays, and further researched the interaction between polycomb repressive complex 2 (PRC2) and BLACAT1 to explore the epigenetic repression of cyclin-dependent protein kinase inhibitors(CKIs), including P15, which may partly account for
Summary
Colorectal cancer is a common cause of cancer death in the world due to late tumor presentation and rapid progression, with about 13 million new cancer cases and 694000 cancer deaths in 2012 worldwide.[1,2] China is one of the countries with high incidence of CRC, in which CRC ranks third among all cancer sites in cancer incidence and fifth in cancer mortality.[3]. Despite the initial controversy regarding their biological characters, increasing evidence had showed that ncRNA are highly regulated and functional.[10,11,12,13] Long intergenic ncRNAs (lincRNA) range in size from several hundred to tens of thousands of bases (⩾200) They belong to a newly discovered class of ncRNAs. more than 3000 human lincRNAs have been identified, less than 1% of them have been characterized.[14] Long noncoding RNAs were initially thought to be spurious transcriptional noise but are emerging as new regulators in the cancer paradigm.[15] emerging evidence indicates that IncRNAs may have complex and extensive functions in the development and progression of cancer. We explored the function of BLACAT1 by using in vitro and in vivo assays, and further researched the interaction between PRC2 and BLACAT1 to explore the epigenetic repression of cyclin-dependent protein kinase inhibitors(CKIs), including P15, which may partly account for
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