Vitamin D May Protect against Breast Cancer through the Regulation of Long Noncoding RNAs by VDR Signaling

Abstract

Dietary vitamin D3 has attracted wide interest as a natural compound for breast cancer prevention and therapy, supported by in vitro and animal studies. The exact mechanism of such action of vitamin D3 is unknown and may include several independent or partly dependent pathways. The active metabolite of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D, calcitriol), binds to the vitamin D receptor (VDR) and induces its translocation to the nucleus, where it transactivates a myriad of genes. Vitamin D3 is involved in the maintenance of a normal epigenetic profile whose disturbance may contribute to breast cancer. In general, the protective effect of vitamin D3 against breast cancer is underlined by inhibition of proliferation and migration, stimulation of differentiation and apoptosis, and inhibition of epithelial/mesenchymal transition in breast cells. Vitamin D3 may also inhibit the transformation of normal mammary progenitors into breast cancer stem cells that initiate and sustain the growth of breast tumors. As long noncoding RNAs (lncRNAs) play an important role in breast cancer pathogenesis, and the specific mechanisms underlying this role are poorly understood, we provided several arguments that vitamin D3/VDR may induce protective effects in breast cancer through modulation of lncRNAs that are important for breast cancer pathogenesis. The main lncRNAs candidates to mediate the protective effect of vitamin D3 in breast cancer are lncBCAS1-4_1, AFAP1 antisense RNA 1 (AFAP1-AS1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), long intergenic non-protein-coding RNA 511 (LINC00511), LINC00346, small nucleolar RNA host gene 6 (SNHG6), and SNHG16, but there is a rationale to explore several other lncRNAs.

Prevalence and Relevance of Vitamin D Deficiency in Newly Diagnosed Breast Cancer Patients: A Pilot Study

“…A possible explanation of how vitamin D might affect breast cancer biology might be the tumor suppressive effects of vitamin D receptor catabolism, as a defect in the vitamin D receptor (e.g., CYP27B1 and CYP24A1 regulation) led to decreased signaling [ 33 ]. In addition, it could be shown that non-coding RNAs (lncRNAs) play an important role in the pathogenesis of breast cancer [ 34 ]. By modulating IncRNA, vitamin D could have a protective effect on the development of breast cancer [ 34 ].…”

“…In addition, it could be shown that non-coding RNAs (lncRNAs) play an important role in the pathogenesis of breast cancer [ 34 ]. By modulating IncRNA, vitamin D could have a protective effect on the development of breast cancer [ 34 ]. However, by now these results could mostly be shown in vitro and in animal experiments, not in clinical trials [ 7 , 8 , 9 ].…”

Vitamin D supplementation improves the prognosis of patients with colorectal cancer liver metastases

“…The role of vitamin D supplementation has been investigated in different cancers [30][31][32][33] . However, its role in CRCLM is poorly understood.…”

“…Our previous publications showed a positive correlation between cancer cell motility and the development of vessel co-option in CRCLM in vivo 12,27,28 , which is mediated by upregulation of runt related transcription factor-1 and actin-related protein 2/3 complex (RUNX1-ARP2/3) pathway 29 . Interestingly, vitamin D has been shown as a negative regulator of cancer cell motility in different types of cancers, such as thyroid 30 , breast 31 , ovarian 32 , and colorectal cancer 33 . The impact of vitamin D on cancer cell motility is yet to be investigated in CRCLM.…”

Calcitriol suppresses gastric cancer progression and cisplatin resistance by inhibiting glycolysis and M2 macrophage polarization through inhibition of mTOR activation

“…demonstrated that calcitriol can modulate cell proliferation, induce apoptosis, and inhibit angiogenesis in various cancer types. [6][7][8] And some clinical trials have been conducted to evaluate its supplements for cancer treatment. [9][10][11] However, its precise effects on the gastric TME and the interplay between macrophages and gastric cancer cells within this context remain poorly understood.…”