Long Non-Coding RNA CCAT1 Acts as a Competing Endogenous RNA to Regulate Cell Growth and Differentiation in Acute Myeloid Leukemia

Abstract

Long non-coding RNAs (lncRNAs) are involved in multiple cellular events, as well as in tumorigenesis. Colon cancer-associated transcript-1 (CCAT1) gene encodes an lncRNA whose over-activation was observed in an expanding list of primary human solid tumors and tumor cell lines, however its biological roles in acute myeloid leukaemia (AML) has not been reported yet at present. In this study, the aberrant upregulation of CCAT1 was detected in French-American-British M4 and M5 subtypes of adult AML patients. By gain- and loss-of-function analysis, we determined that CCAT1 repressed monocytic differentiation and promoted cell growth of HL-60 by sequestering tumor suppressive miR-155. Accordingly, a significant decrease in miR-155 level was detected in AML patients. Re-introduction of miR-155 into HL-60 cells restored monocytic maturation and repressed cell proliferation. Furthermore, CCAT1 could up-regulated c-Myc via its competing endogenous RNA (ceRNA) activity on miR-155. In conclusion, these results revealed new mechanism of lncRNA CCAT1 in AML development, and suggested that the manipulation of CCAT1 expression could serve as a potential strategy in AML therapy.

Long noncoding RNAs: pivotal regulators in acute myeloid leukemia

“…UCA1 silencing by short-hairpin RNA transduction results in a significant reduction of cell proliferation, with an increase in the G1 phase and a decrease in the S phase. Another example is lncRNA CCAT1, which can coordinate the proliferation and differentiation of AML cells [25]. Overexpression and knockdown experiments demonstrate that CCAT1 inhibits the PMA-induced monocytic differentiation as well as promotes the proliferation of AML-derived HL60 cells [25].…”

“…Another example is lncRNA CCAT1, which can coordinate the proliferation and differentiation of AML cells [25]. Overexpression and knockdown experiments demonstrate that CCAT1 inhibits the PMA-induced monocytic differentiation as well as promotes the proliferation of AML-derived HL60 cells [25]. As to apoptosis of AML cells, Xing et al [27] found that HOTAIR knockdown inhibits cell growth and colony formation, and also induces the apoptosis of AML cells [27].…”

“…For example, PVT1 can promote the proliferation of hepatocellular carcinoma and non-small cell lung cancer cells [33, 34]. Similarly, CCAT1 can promote the proliferation and invasion of colon cancer cells, gallbladder cancer cells and hepatocellular carcinoma cells [25, 35, 36]. These observations indicate that such lncRNAs usually share similar functions in leukemia and other types of malignancies.…”

“…BGL3 functions as a competitive endogenous RNA for binding miR-17, miR-93, miR-20a, miR-20b, miR-106a and miR-106b to cross-regulate PTEN expression [24]. CCAT-1 exerts its oncogenic activity by sequestering tumor-suppressive miR-155, an inducer of apoptosis and cell differentiation, which is down-regulated in AML [25, 37]. HOTAIR competitively binds to and sequesters miR-193a, thus modulating the expression of c-KIT in AML cells [27].…”

Identification of lncRNA functions in lung cancer based on associated protein-protein interaction modules

“…Furthermore, lncRNAs can alter the post-transcriptional regulation of mRNA, cellular signaling, and protein activity through allosteric regulation45. Some lncRNAs can act as microRNA sponges to reduce the amount of microRNA available to target genes678. To obtain a better understanding of regulatory networks in cell, it is important to understand the function of each lncRNA.…”