The inhibitory effect of MEG3/miR-214/AIFM2 axis on the growth of T-cell lymphoblastic lymphoma

Abstract

T-cell lymphoblastic lymphoma (T-LBL) is an aggressive malignancy with poor prognosis and high recurrence rate. Long non-coding RNA (lncRNA)-MEG3 is an important tumor suppressor in various cancers. The present study investigated the potential role of maternally expressed gene 3 (MEG3) in the progression of T-LBL. Suppressed expression of MEG3 was detected in T-LBL tissues compared with adjacent histologically normal tissues. Down-regulated level of MEG3 was also found in three T-LBL cell lines (CCRF-CEM, Jurkat and SUP-T1) compared with human T-cell line H9. The proliferation of T-LBL cells was inhibited and cell apoptosis rate was largely promoted when MEG3 was upregulated by a lentiviral vector. Further research revealed that microRNA (miRNA)-214 is a direct target of MEG3. The expression of miR-214 was increased in T-LBL tissues and cell lines compared with control groups. Besides, decreased level of miR-214 was elevated adding miR-214 mimic in SUP-T1 cells transfected with LncRNA-MEG3. Similarly, upregulated level of miR-214 was downregulated adding miR-214 inhibitor in SUP-T1 cells transfected with MEG3 siRNA. Luciferase activity assay further confirmed the targeting relationship between MEG3 and miR-214. Moreover, AIFM2 protein was predicted as a target of miR-214. The expression of AIFM2 was increased by MEG3 and was downregulated by miR-214 mimic. miRNA-214 reversed the effect of MEG3 on inhibiting cell proliferation and inducing cell apoptosis and cell cycle arrest in SUP-T1 cells. Moreover, relative expression of AIFM2 had a positive correlation with the expression of MEG3 and was negatively affected by miR-214. In vivo, MEG3 effectively suppressed tumor growth and the expression of proliferation markers Ki-67 and proliferating cell nuclear antigen (PCNA). Taken together, our research revealed that MEG3 worked as an anti-oncogene in T-LBL, and the MEG3-miR-214-AIFM2 pathway regulated the growth of T-LBL, providing potential prognosis markers as well as new potential targets for T-LBL treatment.

Nucleus‐localized adiponectin is survival gatekeeper through miR‐214‐mediated AIFM2 regulation

“…The expression level of AIFM2 and MEG3 significantly increased in Dox (+) iRS cells (Figure 6d). Furthermore, miR-214-3p, which is a microRNA inversely associated with MEG3 in a post-transcriptional manner (Fan et al, 2017), significantly decreased in Dox (+) iRS cells as detected by miRNA qPCR analyses (Figure 6d). No significant change of miR-214-5p between Dox (−) and Dox (+) iRS cells was detected (Supporting Information Figure S5).…”

LINC00221 suppresses the malignancy of children acute lymphoblastic leukemia

“…As is revealed by Pouyanrad et al [25], miR-335-3p is sponged by NEAT1 and MALAT1 and is associated with poor prognosis in ALL through targeting ABCA3. MEG3 served as an anti-oncogene in T-cell lymphoblastic lymphoma through MEG3/miR-214/AIFM2 pathway [26]. LncRNA SNHG16 sponges miR-497-5p and elevates PIM1 expression, boosting cell proliferation and suppressing apoptosis in diffuse large B-cell lymphoma cells [27].…”

6mer seed toxicity in viral microRNAs

“…While there was no v-miRNA with the same 6mer seed as miR-34a-5p, we found a v-miRNA that shared the same 2-7 nucleotides present in the predominant 5p arm of the miR-15/16-5p miRNA family. kshv-miR-K12-6-5p (miR-K12-6-5p) contains a GC-rich trinucleotide repeat seed sequence that is found in three miRNA families with ample published evidence for having tumor suppressive activities: miR-15/16-5p (Bonci et al, 2008;Calin et al, 2008;Calin et al, 2002;Han et al, 2017;Hu et al, 2018;Huang et al, 2015;Ke et al, 2013;Klein et al, 2010;Lovat et al, 2015;Lovat et al, 2018;Maximov et al, 2019;Pekarsky and Croce, 2015;Rahman et al, 2014;Yang et al, 2014), miR-214-3p (Cagle et al, 2019;Fan et al, 2017;Huang et al, 2014;Liu et al, 2016;Long et al, 2015;Pang et al, 2018;Phatak et al, 2016;Wang et al, 2012;Yang et al, 2015;Yang et al, 2018b;Zhang et al, 2017), and miR-103/107-3p Feng et al, 2012;Fu et al, 2019;Gao et al, 2017;Piao et al, 2012;Sharma et al, 2017;Song et al, 2015;Yamakuchi et al, 2010;Yang et al, 2018a;Zhang et al, 2019) (Figure 2A). miR-K12-6-5p shares an 8mer seed sequence with miR-15a-5p, miR-15b-5p, and miR-16-5p, and a 6, 7 or 8mer seed with other members of this family (Figure 2A).…”