Abstract
BackgroundmicroRNA Let-7 serves as a tumor suppressor by targeting various oncogenic pathways in cancer cells. However, the underlying mechanism of its involvement in breast cancer remains largely unknown. With our research, our endeavor is to explore the role of the CDX2/let-7b/COL11A1 axis in breast cancer cell activities.MethodsTumor tissues and adjacent normal tissues were collected from 86 patients with breast cancer. Human breast cancer epithelial cell line MCF-7 was treated with over-expressed CDX2, let-7b mimic, shRNA against COL11A1 and their negative controls. The expression of CDX2, let-7b, and COL11A1 in the tissues and cells was determined by RT-qPCR. Interactions among CDX2, let-7b, and COL11A1 were detected by ChIP and dual-luciferase reporter assay, respectively. After different transfections, cell invasion, migration, and proliferation abilities were determined by Transwell and EdU assays. Lastly, tumor xenografts in nude mice were established and hematoxylin and eosin staining was performed to assess the tumor growth and lymph node metastasis.ResultsCDX2 and let-7b were poorly expressed in breast cancer cells and tissues. CDX2 bound to let-7b and promoted the expression of let-7b, which contrarily inhibited the expression of COL11A1. Cancer cell proliferation, invasion, migration, and metastasis were stimulated when CDX2 and let-7b were depleted or COL11A1 was over-expressed. Xenograft tumors growth and metastasis were in accordance with the results of cellular experiments.ConclusionIn agreement with these observations, we could reach a conclusion that CDX2 could promote let-7b expression, which may exert an inhibitory effect on the proliferation, migration, and metastasis of breast cancer cells via repressing the expression of COL11A1, providing a novel therapeutic strategy for the treatment of metastatic breast cancer.
Highlights
MicroRNA Let-7 serves as a tumor suppressor by targeting various oncogenic pathways in cancer cells
caudal type homeobox 2 (CDX2) is poorly expressed in breast cancer, while over‐expressed CDX2 inhibits migration and invasion of breast cancer epithelial cells As compared to adjacent normal tissues, CDX2 expression was decreased in breast cancer tissues, and the CDX2 protein was located at the nucleus and stained in brown (p < 0.05; Fig. 1a–c)
The expression of CDX2 was diminished in human breast cancer epithelial cell lines MCF-7 and MDA-MB-231 compared to that of normal human breast epithelial cell line HBL-100, where the MCF-7 cell line exhibited the lowest expression of CDX2 (p < 0.05; Fig. 1f )
Summary
MicroRNA Let-7 serves as a tumor suppressor by targeting various oncogenic pathways in cancer cells. Transcriptional factors are well-known to play critical roles in numerous human diseases including cancers, Wang et al Cancer Cell Int (2020) 20:13 and regarded as key regulators for new therapies [5]. One such factor, caudal type homeobox 2 (CDX2), a member of the caudal-related homeobox gene family and a mediator of apoptosis in tissues, was found in intestinal epithelial cells [6]. This study distinguishes from other studies by emphasizing the role of transcriptional factors and miRNAs in the invasion, migration, and metastasis of breast cancer epithelial cells
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