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A non‐canonical tumor suppressive role for the long non‐coding RNA MALAT1 in colon and breast cancers
Author(s) -
Kwok Zhi Hao,
Roche Veronique,
Chew Xiao Hong,
Fadieieva Anastasiia,
Tay Yvonne
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31386
Subject(s) - malat1 , pten , biology , carcinogenesis , transcriptome , microrna , long non coding rna , crosstalk , cancer research , suppressor , gene , metastasis , rna , genetics , cancer , gene expression , pi3k/akt/mtor pathway , signal transduction , physics , optics
Long noncoding RNAs (lncRNAs) constitute one of the largest classes of transcripts and have been widely implicated in various diseases such as cancer. Increasing evidence suggests that several lncRNAs are dysregulated and play critical roles in tumorigenesis. LncRNAs can be regulated by key oncogenes and tumor suppressors, adding complexity to the intricate crosstalk between protein coding genes and the noncoding transcriptome. In our study, we investigated the effect that dysregulation of the key tumor suppressor PTEN has on the noncoding transcriptome. We identified the lncRNA metastasis associated lung adenocarcinoma transcript 1 ( MALAT1 ) as a target of PTEN and find that this regulation is conserved in both human and mouse as well as with both chronic and acute PTEN dysregulation. We show that this regulation is at least in part microRNA (miRNA)‐dependent, and characterize the miRNAs that may be mediating this crosstalk. In summary, we establish and characterize a non‐canonical PTEN‐ microRNA ‐ MALAT1 axis that regulates tumorigenesis and describe for the first time that the MALAT1 lncRNA possesses novel tumor suppressive properties in colon and breast cancers.