Malignant tumors are heterogeneous diseases characterized by uncontrolled cell proliferation, invasion, metastasis, and/or recurrence of their malignancies. In particular, cancer stem cells (CSCs) within these tumors might be responsible for the property of invasiveness and/or therapies-resistance. CSCs are a self-renewing, awfully tumorigenic subpopulation of cancer cells, which are notorious for strong chemoresistance and are frequently responsible the aggravated invasion, metastasis, and/or recurrence. Developing targeting therapies against CSCs, therefore, may be deliberated a more encouraging mission for the greater cancer therapy. Innovation for a more potent anti-CSC treatment has been required as soon as possible. Interestingly, vitamin D could modulate the inflammatory condition of the tumor microenvironment (TME) by successfully affecting CSCs, which has an imperative role in determining the malignant phenotype of CSCs. In addition, vitamin D may also contribute to the regulation of the malignant behaviors of CSCs. Consistently, vitamin D could have potential applications for the significant inhibition of several tumor growths within various cancer therapies. The biological significance of vitamin D for CSCs regulation may be involved in the function of APRO family proteins. Therefore, vitamin D could be one of the innovative therapeutic modalities for the development of novel CSCs related tumor therapies.

The non-coding RNAs (ncRNAs) are a family of single-stranded RNAs that have become recognized as crucial gene expression regulators in normal and cancer cell biology. The gut microbiota, which consists of several different bacteria, can actively contribute to the regulation of host metabolism, immunity, and inflammation. Roles of ncRNAs and gut microbiota could significantly interact with each other to regulate the growth of various types of cancer. In particular, a causal relationship among ncRNAs, gut microbiota, and immune cells has been shown for their potential importance in the development of breast cancer. Alteration of ncRNA expression and/or gut microbiota profiles could also influence several intracellular signaling pathways with the function of anti-proliferative (APRO) family proteins associated with the malignancy. Targeting ncRNAs and/or APRO family proteins for the treatment of various cancers has been revealed with novel immune therapies. Here, the most recent studies to underline the key role of ncRNAs, APRO family proteins, and gut microbiota in breast cancer progression have been discussed. For more effective breast cancer therapy, it would be imperative to figure out the collective mechanism of ncRNAs, APRO family proteins, and gut microbiota.