Data from: Malat1 as an evolutionarily conserved lncRNA, plays a positive role in regulating proliferation and maintaining undifferentiated status of early-stage hematopoietic cells

Background: The metastasis-associated lung adenocarcinoma transcription 1
(Malat1) is a highly conserved long non-coding RNA (lncRNA) gene. Previous
studies showed that Malat1 is abundantly expressed in many tissues and
involves in promoting tumor growth and metastasis by modulating gene
expression and target protein activities. However, little is known about
the biological function and regulation mechanism of Malat1 in normal cell
proliferation. Results: In this study we conformed that Malat1 is highly
conserved across vast evolutionary distances amongst 20 species of mammals
in terms of sequence, and found that mouse Malat1 expresses in tissues of
liver, kidney, lung, heart, testis, spleen and brain, but not in skeletal
muscle. After treating erythroid myeloid lymphoid (EML) cells with
All-trans Retinoic Acid (ATRA), we investigated the expression and
regulation of Malat1 during hematopoietic differentiation, the results
showed that ATRA significantly down regulates Malat1 expression during the
differentiation of EML cells. Mouse LRH (Lin-Rhodamine low Hoechst low )
cells that represent the early-stage progenitor cells show a high level of
Malat1 expression, while LRB (Lin − Hoechst Low Rhodamine Bright ) cells
that represent the late-stage progenitor cells had no detectable
expression of Malat1. Knockdown experiment showed that depletion of Malat1
inhibits the EML cell proliferation. Along with the down regulation of
Malat1, the tumor suppressor gene p53 was up regulated during the
differentiation. Interestingly, we found two p53 binding motifs with help
of bioinformatic tools, and the following chromatin immunoprecipitation
(ChIP) test conformed that p53 acts as a transcription repressor that
binds to Malat1’s promoter. Furthermore, we testified that p53 over
expression in EML cells causes down regulation of Malat1. Conclusions: In
summary, this study indicates Malat1 plays a critical role in maintaining
the proliferation potential of early-stage hematopoietic cells. In
addition to its biological function, the study also uncovers the
regulation pattern of Malat1 expression mediated by p53 in hematopoietic
differentiation. Our research shed a light on exploring the Malat1
biological role including therapeutic significance to inhibit the
proliferation potential of malignant cells.