LINC00265/miR-4500 Axis Accelerates Acute Lymphoblastic Leukemia Progression by Enhancing STAT3 Signals

Abstract

Background Long noncoding RNA LINC00265 or miR-4500 is involved in the pathogenesis of many cancers. However, their functions in acute lymphoblastic leukemia (ALL) remain unknown. In this study, we investigated how LINC00265 and miR-4500 regulate the malignant characteristics of ALL. Methods Real-time PCR was used in examining the expression of LINC00265 in ALL cell lines and blood of patients with ALL. Cell proliferation, cell migration, and xenograft tumor assays were performed to verify the function of LINC00265 subjected to overexpressing and silencing experiments. The ceRNA mechanism with LINC00265/miR-4500/STAT3 was investigated through luciferase and RNA pull-down assays. Finally, the function of the LINC00265/miR-4500/STAT3 axis subjected to overexpressing and silencing assays was determined through cell proliferation, cell migration, and xenograft tumor assays. Results LINC00265 was highly expressed in ALL cell lines and blood of patients with ALL and facilitated the proliferation, migration, invasion, and growth of xenograft tumors of ALL cells. The silencing of LINC00265 expression with LINC00265 siRNA significantly inhibited the malignancy of the ALL cells. RNA pull-down and luciferase assays demonstrated that LINC00265 competitively targeted miR-4500 and enhanced STAT3 expression. Furthermore, miR-4500 inhibitors or overexpressed LINC00265 up-regulated STAT3 expression, and miR-4500 mimics or STAT3 shRNAs eliminated the LINC00265-induced malignancy of the ALL cells. Conclusion Mechanistically, LncRNA LINC00265 can competitively interact with miR-4500 and thereby up-regulates STAT3 signaling and enhances the malignancy of tumors.

Silencing of the long non-coding RNA <i>LINC00265</i> triggers autophagy and apoptosis in lung cancer by reducing protein stability of SIN3A oncogene

“…Consistent with this conclusion, it has been shown that the SIN3A promotes cell survival in different cancers by forming a complex with STAT3 to silence tumor repressor genes [ 21 ]. Interestingly, LINC00265 has been also shown to promote metastasis of acute lymphoblastic leukemia by regulating STAT3 signaling [ 14 ]. This raises a possibility that LINC00265 cooperates with SIN3A to enhance STAT3 signaling in LUAD.…”

“…It is upregulated in colorectal cancer (CRC) and associated with poor prognosis [ 9 – 11 ]. Higher levels of LINC00265 were also found in the serum of patients with acute myeloid leukemia (AML), which is correlated with lower overall survival rate because LINC00265 contributes to migration and invasion of tumor cells by regulating PI3K/AKT and signal transducer and activator of transcription 3 (STAT3) signaling [ 12 – 14 ]. Therefore, circulating LINC00265 can be used as a biomarker for diagnosis and therapeutic monitoring of AML [ 15 ].…”

Curcumin in treatment of hematological cancers: Promises and challenges

“… 46 LINC00265 sponges miRNA-4500 to mediate STAT3 in proliferation and metastasis of leukemia cells. 47 STAT3 upregulates MYC to facilitate viability of leukemia stem cells. 48 Based on these examples, STAT3 signaling activation causes tumorigenesis.…”