<p>Lung Cancer Cells Derived Circulating miR-21 Promotes Differentiation of Monocytes into Osteoclasts</p>

Abstract

Osteoclastogenesis is a key process in osteolytic bone metastasis (BM). Previous studies indicated that some miRNAs could regulate cancers progression and osteoclastogenesis. Our purpose was to investigate the roles of lung cancer cells-derived circulating miR-21 on osteoclastogenesis and its clinical significance in BM patients. Materials and Methods: The difference of miRNA expression in two lung cancer cell lines SBC-5 (with characteristic BM ability) and SBC-3 (without BM ability) were analyzed by microarray and qRT-PCR. Circulating miR-21 levels of lung cancer patients with or without BM were compared by qRT-PCR. The TRAP staining was used to investigate the effects of conditioned media from lung cancer cell lines or patients' plasma with different miR-21 levels on osteoclastogenesis. ROC curve was used to evaluate the diagnostic performance of circulating miR-21 in BM patients. Results: We found that miR-21 expression was specifically higher in SBC-5 than that in SBC-3 cells. The supernatants of SBC-5 cells with higher-level miR-21 promoted osteoclastogenesis. Moreover, we demonstrated that the circulating miR-21 level was significantly higher in BM patients than that in non-BM patients. The plasma from BM patients with higher-level miR-21 could also promote osteoclastogenesis. Mechanistically, lung cancer cells-derived circulating miR-21 could be transferred into osteoclast precursor cells and promote osteoclastogenesis probably by inhibiting PTEN. Finally, clinical data showed that circulating miR-21 had a potential for the diagnosis of BM. Conclusion: Overall, our findings suggested that circulating miR-21 played important roles in osteoclastogenesis of lung cancer patients and may serve as a biomarker to diagnose BM of lung cancer.

Breast cancer exosomes contribute to pre-metastatic niche formation and promote bone metastasis of tumor cells

“…miR-21, a highly conserved oncomicroRNA, is expressed in serum of many types of cancer patients, including hepatocellular carcinoma, lung cancer, and breast cancer, which is significantly higher than that in healthy controls 29 - 31 . Several studies demonstrate that miR-21 involves in tumor progression and osteoclasts differentiation 32 , 33 . For example, miR-21 promotes NFATc1 up-regulation during osteoclast differentiation by directly binding programmed cell death 4 (PDCD4), which has a suppressive function on c-Fos transactivation 34 .…”

Regulation of Osteoclastogenesis and Bone Resorption by miRNAs

“…The pro-osteoclastic function of miR-21 is further demonstrated in vivo using miR-21 knockout mice, in which miR-21 deficiency inhibits bone resorption and osteoclastogenesis via targeting PDCD4 (Hu et al, 2017). miR-21 is found to be downregulated by bisphosphonate in lung cancer patients with osteolytic bone metastasis (Zhao et al, 2020). Another study revealed that estrogen suppresses miR-21 biogenesis, leading to upregulation of Fas Ligand (FasL), which is a target of miR-21 in osteoclasts and induces osteoclast cell death in an autocrine manner (Sugatani and Hruska, 2013).…”

Triple Negative Breast Cancer: A Mountain Yet to Be Scaled Despite the Triumphs

“…In accordance with this, Dong and colleagues indicated that PTEN, a pro-apoptotic factor, is down-regulated when the miR-21 expression is enhanced in TNBC cell line. Additionally, miR-21 has shown to be associated with tumorigenesis and differentiation of osteoclast [179,180]. The miR-21 exhibit its negative effects by targeting programmed cell death 4 protein (PDCD4).…”