<p>MiR-153-5p Enhances the Sensitivity of Triple-Negative Breast Cancer Cells to Paclitaxel by Inducing G2M Phase Arrest</p>

Abstract

Background: Paclitaxel (PTX) resistance is a main obstacle for the treatment of triplenegative breast cancers (TNBC). Evidences have shown that miR-153-5p could induce the apoptosis of breast cancer cells. Thus, this study aimed to investigate the effect of miR-153-5p on PTX-resistance TNBC cells. Methods: Cell Counting Kit-8, flow cytometry and wound healing assays were used to detect the viability, apoptosis and migration of MDA-MB-231/PTX cells, respectively. The luciferase reporter assay was used to explore the potential binding targets of miR-153-5p. The expressions of CDK1, cyclin B1 and p-Akt in MDA-MB-231/PTX cells were detected with Western blot. In vivo animal study was performed finally. Results: In this study, the inhibitory effects of PTX on the proliferation and migration of MDA-MB-231/PTX cells were significantly enhanced following transfection with miR-153-5p. In addition, overexpression of miR-153-5p markedly enhanced the pro-apoptotic effect of PTX on MDA-MB-231/PTX cells. Luciferase reporter assay validated that cyclin-dependent kinase 1 (CDK1) was a potential binding target of miR-153-5p. Moreover, overexpression of miR-153-5p prominently increased PTX-induced cell cycle arrest at G2/M phase in MDA-MB-231/PTX cells via downregulation of CDK1, cyclin B1 and p-Akt. In vivo experiments confirmed that overexpression of miR-153-5p notably enhanced PTX sensitivity in MDA-MB-231/PTX xenograft model. Conclusion: We found that overexpression of miR-153-5p could reverse PTX resistance in PTX-resistant TNBC cells via inducing G2/M phase arrest, indicating that miR-153-5p may be a promising agent for patients with PTX-resistant TNBC.

miR-153-5p suppresses the proliferation, invasion and migration of malignant meningioma via the MEK/ERK signaling pathway by targeting GAB1

“…Many studies have shown that miR-153-5p, as a tumor suppressor gene, contributes to the development of various malignant tumors. Overexpression of miR-153-5p has been shown to enhance the drug sensitivity of breast cancer cells to paclitaxel, inhibit the proliferation and migration of breast cancer cells, and promote apoptosis of breast cancer cells 35 . In another study, miR-153 expression was lower in ovarian cancer than in adjacent tissues, which inhibited the proliferation and invasion of ovarian cancer cells and decreased their tumorigenesis potential 36 .…”

“…It has been revealed recently that several miRNAs, such as miRNA-200a, miRNA-145, or miRNA-224, are expressed aberrantly in meningioma 8 . miRNA microarrays have demonstrated that abnormal miRNA expression may act as potential diagnostic and prognostic biomarkers for cancer 9,10 , and many potential miRNAs were used as diagnostic biomarkers and therapeutic targets for meningiomas [11][12][13] . MiR-153-5p is a newly discovered small-molecule coding RNA.…”

“…MiR-153-5p is a newly discovered small-molecule coding RNA. Recently, studies have exhibited that MiR-153-5p participates in the onset and progress of various tumors for instance, renal cell carcinoma 14 , breast cancer 15 , and colorectal cancer 16 . It has also been shown that miR-153-5p over-expression enhanced the dampening in uence of sh-HOTAIRM1 transfection on migration along with in ltration in glioblastoma 17 , which illustrates miR-153-5p plays an indispensable role in the onset and progress of the malignant tumor in the central nervous system.…”

A comprehensive review on miR-153: Mechanistic and controversial roles of miR-153 in tumorigenicity of cancer cells

“…The studies have revealed that an increase in AKT expression can be contributed to downregulation of miR-153. However, overexpression of miR-153 induces cell cycle arrest in G0/G1 and G2/M phases as well as inhibiting proliferation by regulating the expression of AKT, CDK1 through binding to and degrading their mRNAs (3,23,24,26). Moreover, miR-153 suppresses the AKT signaling pathway in glioblastoma through reduction in expression of insulin receptor substrate-2 (Irs-2) which acts as a molecular adaptor, mediating influences of insulin and insulinlike growth factor 1 (IGF-1) on cell proliferation (Figure 1) (27).…”

“…However, high expression level of miR-153 increases sensitivity of cancer cells to radiotherapy, which may be mediated by targeting Snail and Jagged canonical notch ligand1 (J AG1) in panc reatic canc er (7 0, 71 ). Moreover, downregulation of miR-153 has been reported in drug resistant cancer cells, whereas miR-153 overexpression enhances the sensitivity of cancer cells to chemotherapy (26,35,76). One of the suggested mechanisms of drug resistance of cancer cells is upregulation of ABCE1 due to downregulation of miR-153 in lung cancer cells (72).…”