Leukemia is a hematologic disease in which cells are blocked at a certain stage of hematopoietic differentiation and display a high proliferative capacity [
7,
33]. Recently, increasing evidence has suggested that lncRNAs are involved in fundamental biological processes, such as cell proliferation, survival, and differentiation [
14,
18]. In this study, we reveal for the first time that the lncRNA PVT1 is significantly upregulated in primary APL cells. Additionally, we provide evidence that upregulated PVT1 expression is involved in the proliferation of APL cells.
More recently, the lncRNA PVT1 has been shown to be dysregulated in several cancers, and it has been functionally linked to cancer tumorigenesis [
34‐
37]. PVT1 is an lncRNA (1.9 kb) and host gene for several miRNAs [
38]. Although there are a few reports demonstrating that PVT1 plays an important role in the pathogenesis of several cancers, it is not yet clear whether PVT1 is involved in the regulation of APL, which is a unique subtype of acute myeloid leukemia (AML) that results from a blockade in granulocyte differentiation during the promyelocytic stage. Here, we found that PVT1 expression is elevated in APL, and its expression is repressed during ATRA-induced differentiation and cell cycle arrest.
c-myc and PVT1 were located on chromosome 8q24; gain of supernumerary copies of the 8q24 chromosomal region in human APL may led to increased copy number of PVT1 in APL. In addition to a gain in 8q24, the well-known MYC protein is a transcriptional activator of PVT1 [
32] and increased in human APL [
31], and it has been reported that treating APL cells with ATRA inhibits the expression of
c-myc mRNA [
39], suggesting that elevated PVT1 expression may also result from MYC protein activation in APL cells. Similarly, in our study,
c-myc knockdown led to PVT1 downregulation. Interestingly, PVT1 inhibition could attenuate the proliferation of APL cells, indicating that PVT1 is essential for APL progression. A recent study has found that PVT1 increases NOP2 levels by enhancing the stability of the NOP2 protein in hepatocellular carcinoma and that the function of PVT1 in cell proliferation is dependent on the presence of NOP2 [
34]. More importantly, a recent report has also highlighted the involvement of PVT1 in regulating MYC, which has been firmly established to play a role in cancer [
40]. Indeed, we confirmed that PVT1 depletion causes a reduction in the MYC protein level in APL. Thus, PVT1 may influence the stability of these important proteins, which are indispensable for APL cell growth. It is therefore possible that PVT1 could be a novel biomarker for APL diagnosis, prognosis, and targeted therapy [
41].
In conclusion, we demonstrated that abnormal elevated expression of the lncRNA PVT1 may be correlated with APL cell proliferation. This is, to our knowledge, the first report of a potential role for the lncRNA PVT1 in APL. These findings provide new insight into the mechanism of APL progression.