MicroRNA‑93 knockdown inhibits acute myeloid leukemia cell growth via inactivating the PI3K/AKT pathway by upregulating DAB2

Abstract

Acute myeloid leukemia (AML) is associated with a poor prognosis in elderly adults and currently lacks optimal treatment strategies. MicroRNAs (miRNAs or miRs) have increasingly been reported to be associated with AML progression; however, the mechanisms of action of miR-93 in AML with the involvement of disabled 2 (DAB2) are currently unknown. In the present study, miR-93 expression was assessed in patients with AML and in AML cell lines. The association between miR-93 expression and the pathological characteristics of patients with AML was analyzed. AML cells were then transfected to knockdown or overexpress miR-93 in order to elucidate its function in AML progression. The target gene of miR-93 was assessed using a dual-luciferase reporter gene assay. The expression levels of miR-93, DAB2 and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway-related proteins were measured and in vivo experiments were conducted to confirm the results. It was observed that miR-93 was highly expressed in patients with AML and in AML cells. The knockdown of miR-93 in HL-60 cells inhibited AML cell proliferation and resistance to apoptosis, while the overexpression of miR-93 in THP-1 cells led to contrasting results. Moreover, miR-93 targeted DAB2 to inactivate the PI3K/AKT pathway, and the overexpression of DAB2 reversed the effects of miR-93 on THP-1 cell growth. Tumor volume, tumor weight, and the positive expression of Ki67, survivin and p53 were increased in THP-1 cells overexpressing miR-93. On the whole, the present study demonstrates that miR-93 is highly expressed in AML cells, and that the suppression of miR-93 inhibits AML cell growth by targeting DAB2 and inhibiting the PI3K/AKT pathway.

Disabled-2: a protein up-regulated by high molecular weight hyaluronan has both tumor promoting and tumor suppressor roles in ovarian cancer

“…DAB2 has previously been found to reduce cell proliferation and in vivo tumorigenicity in SKOV3 ovarian cancer cells [ 7 ]. This is consistent with other studies in acute myeloid leukaemia, breast cancer, lung, and hepatocellular cancers where DAB2 inhibited cell proliferation [ 24 , 61 , 64 , 78 ]. Enhanced proliferation and in vivo tumorigenicity by DAB2 has also been observed in urothelial and prostate cancer highlighting the need for further studies [ 26 , 73 ].…”

Disabled-2: a protein up-regulated by high molecular weight hyaluronan has both tumor suppressor and tumor promoting roles in ovarian cancer

“…DAB2 has previously been found to reduce cell proliferation and in vivo tumorigenicity in SKOV3 ovarian cancer cells(63). This is consistent with other studies in acute myeloid leukaemia, breast cancer, lung, and hepatocellular cancers where DAB2 inhibited cell proliferation (66, 70,74,75). Enhanced proliferation and in vivo tumorigenicity by DAB2 has also been observed in urothelial and prostate cancer highlighting the need for further studies (59,76).…”

Disabled-2: a protein up-regulated by high molecular weight hyaluronan has both tumor promoting and tumor suppressor roles in ovarian cancer

“…DAB2 has previously been found to reduce cell proliferation and in vivo tumorigenicity in SKOV3 ovarian cancer cells [6]. This is consistent with other studies in acute myeloid leukaemia, breast cancer, lung, and hepatocellular cancers where DAB2 inhibited cell proliferation [22,56,59,73]. Enhanced proliferation and in vivo tumorigenicity by DAB2 has also been observed in urothelial and prostate cancer highlighting the need for further studies [24,68].…”