miR-362-5p promotes cell proliferation and cell cycle progression by targeting GAS7 in acute myeloid leukemia

Abstract

Recently, miR-362-5p has attracted special interest as a novel prognostic predictor in acute myeloid leukemia (AML). However, its biological function and underlying molecular mechanism in AML remain to be further defined. Herein, we found that a significant increase in miR-362-5p expression was observed in AML patients and cell lines using quantitative realtime PCR. The expression of miR-362-5p was altered in THP-1 and HL-60 cells by transfecting with miR-362-5p mimic or inhibitor. A series of experiments showed that inhibition of miR-362-5p expression significantly suppressed cell proliferation, induced G0/G1 phase arrest and attenuated tumor growth in vivo. On the contrary, ectopic expression of miR-362-5p resulted in enhanced cell proliferation, cell cycle progression and tumor growth. Moreover, growth arrest-specific 7 (GAS7) was confirmed as a direct target gene of miR-362-5p and was negatively modulated by miR-362-5p. GAS7 overexpression imitated the tumor suppressive effect of silenced miR-362-5p on THP-1 cells. Furthermore, miR-362-5p knockdown or GAS7 overexpression obviously down-regulated the expression levels of PCNA, CDK4 and cyclin D1, but up-regulated p21 expression. Collectively, our findings demonstrate that miR-362-5p exerts oncogenic effects in AML by directly targeting GAS7, which might provide a promising therapeutic target for AML.

LncRNA GAS5 sponges miR‐362‐5p to promote sensitivity of thyroid cancer cells to 131I by upregulating SMG1

“…Yang et al validated that GAS5 elevation inhibited viability and facilitated apoptosis of PC cells, and also modulated α‐Solanine‐triggered radiosensitivity 9 . Moreover, it has been reported that upregulated miR‐362‐5p accelerated bladder cancer cell proliferation, 23 and miR‐362‐5p was revealed to promote AML cell proliferation and cell cycle progression 14 . In addition, our in vivo experiment suggested that GAS5 overexpression could decelerate tumor growth in a TC nude mouse model.…”

“…9 Moreover, it has been reported that upregulated miR-362-5p accelerated bladder cancer cell proliferation, 23 and miR-362-5p was revealed to promote AML cell proliferation and cell cycle progression. 14 In addition, our in vivo experiment F I G U R E 7 GAS5 inactivates the Akt/mTOR signaling pathway by mediating the miR-362-5p/SMG1 axis. (a,b), expression of Akt and mTOR in parent cells and 131 I-resistant TC cells was assessed by Western blot analysis; one-way ANOVA was used for comparisons among multiple groups, followed by Tukey's post hoc test; **, p<.01 suggested that GAS5 overexpression could decelerate tumor growth in a TC nude mouse model.…”

“…10 Certain miRNAs such as miR-335-5p 11 and miR-429 12 were involved in TC. MiR-362-5p is a miRNA usually functioning as an oncogene in human cancers, 13,14 while its role in TC progression and interaction between GAS5 and miR-362-5p remains to be further investigated. Belonging to the phosphoinositide 3-kinase-related kinases PIKK family, suppressor of morphogenesis in genitalia 1 (SMG1) has been demonstrated to be involved in the progression of pancreatic cancer 15 and nasopharyngeal carcinoma (NPC), 16 whereas it has been seldom explored in TC.…”

Characterization of Hepatitis B Virus Integrations Identified in Hepatocellular Carcinoma Genomes

“…We identified HBV integrations with high integration allele fraction seven non-recurrent cancer-related genes, including GAS7 [74,75], NS [77,78], NRG1 [79], PRDM16 [80], ARID1B [81], and AFF1 [82]. GAS7 has be directly regulated by P53 and is part of a critical mechanism that mediate metastasis [74]; NRG1 fusions were identified as drivers for lung adenoc…”

“…We identified HBV integrations with high integration allele fractions in tumors in seven non-recurrent cancer-related genes, including GAS7 [ 74 , 75 ], NSP [ 76 ], RSPO2 [ 77 , 78 ], NRG1 [ 79 ], PRDM16 [ 80 ], ARID1B [ 81 ], and AFF1 [ 82 ]. GAS7 has been shown to be directly regulated by P53 and is part of a critical mechanism that mediates breast cancer metastasis [ 74 ]; NRG1 fusions were identified as drivers for lung adenocarcinoma [ 79 ]; And the involvement of PRDM16 in leukemia [ 80 ], ARID1B in ovarian cancer [ 81 ], and AFF1 in leukemia [ 82 ] has also been reported; It has been demonstrated that a GAS7 -mediated pathway suppressed proliferation of HCC cells following treatment with oxaliplatin, an alkylating anti-neoplastic agent, and the inhibition of GAS7 negated the beneficial effects of the drug [ 83 ].…”