<p>microRNA-628 inhibits the proliferation of acute myeloid leukemia cells by directly targeting IGF-1R</p>

Abstract

BackgroundA variety of microRNAs (miRNAs) are aberrantly expressed in acute myeloid leukemia (AML), and these dysregulated miRNAs perform crucial roles in tumorigenesis and progression of AML. miR-628-3p (miR-628), one of the miRNAs dysregulated in multiple types of human cancers, exerts antitumor roles in different cancer types. However, no specific study has explored the expression pattern and role of miR-628 in AML.Materials and methodsIn this study, RT-qPCR was performed to detect miR-628 expression in AML tissues and cell lines. CCK-8 assay, flow cytometry analysis and xenograft tumor experiment was carried out to determine the functions of miR-628 in AML cells. The possible mechanism underlying the activity of miR-628 in AML cells was also explored using a series of experiments.ResultsOur results revealed the downregulated expression of miR-628 in patients with AML and AML cell lines. Ectopic expression of miR-628 resulted in the inhibition of AML cell proliferation and induction of cell cycle arrest and apoptosis in vitro and attenuation of tumor growth in vivo. Insulin-like growth factor 1 receptor (IGF-1R) was identified as a direct target gene of miR-628 in AML cells. IGF-1R expression was upregulated in patients with AML and upregulation of IGF-1R expression inversely correlated with miR-628 level. Furthermore, IGF-1R knockdown imitated the tumor suppressive effect of miR-628 in AML cells. Restoration of IGF-1R expression abrogated the effects of miR-628 on the proliferation, cycle status, and apoptosis rate of AML cells. miR-628 inhibited the activation of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt) pathway in AML cells both in vitro and in vivo through the inhibition of IGF-1R expression.ConclusionOur results demonstrate that miR-628 exhibits antitumor effects in AML through the direct targeting of IGF-1R and regulation of PI3K/Akt pathway, suggestive of its potential role as a therapeutic target in patients with this aggressive hematological malignant tumor.

<p>Long noncoding RNA SNHG16 silencing inhibits the aggressiveness of gastric cancer via upregulation of microRNA-628-3p and consequent decrease of NRP1</p>

“…In recent years, miR-628-3p (miR-628) was reported to substantially participate in the progression of several types of human cancer, including colorectal cancer,20 acute myeloid leukemia,21 pancreatic cancer,22 and non-small-cell lung cancer 23. Nevertheless, whether the expression profile of miR-628 is altered in gastric cancer remains unclear and whether its aberrant expression is important for the aggressiveness of gastric cancer is yet to be studied.…”

MicroRNA‑628‑5p inhibits cell proliferation and induces apoptosis in colorectal cancer through downregulating CCND1 expression levels

“…Therefore, it was hypothesized that mir-628-5p is a tumor suppressor for colorectal cancer. mir-628-5p decreased the tumorigenicity of epithelial ovarian cancer cells (44), and mirna-628 inhibited the proliferation of acute myeloid leukemia cells (14). in addition, mir-628 .…”

“…Previous studies have demonstrated that mirnas serve an important role in the development of tumors; the aberrant overexpression or downregulation of multiple mirnas are often detected in a variety of tumors, suggesting that mirnas have different roles in different processes, such as tumor occurrence, development and metastasis (11,12). Previous studies have reported the abnormal expression of mirna (mir)-628 in numerous malignant tumor tissues (13,14); however, there are few studies observing the effects of mir-628 in colorectal cancer.…”

Role of PI3K/AKT pathway in cancer: the framework of malignant behavior

“…Secondly, PTEN plays critical roles in regulating not only hematopoietic stem cell activity through a Niche-dependent mechanism, but also hematopoiesis and leukemogenesis [341][342][343]. Furthermore, TAL1, c-Jun, EZH2, TRIM22, ETV6/RUNX1, miR-7, -22, -26b, -103, -125b, -126, -139-5p, -181c, -193a, -628, and -3142, as well as LncRNA HULC, UCA1, linc00239 and LINC00265 control leukemogenesis, proliferation, apoptosis or chemoresistance via PI3K/AKT pathway [344][345][346][347][348][349][350][351][352][353][354][355][356][357][358][359][360][361][362][363]. Hereafter, PI3K/AKT pathway inhibition is regarded as a therapeutic approach [364,365] followed by the preclinical studies in leukemia cells [366,367] in spite of the upregulated expression of P2RY14 in acute leukemia cells resistant to PI3K/ mTOR inhibition [368].…”