Table 3 Functional evidence of vitamin D and vitamin D Receptor (VDR) signaling pathways linked to long noncoding RNAs (lncRNAs)

Treatment with 1α,25(OH)₂D₃

Ovarian cancer cell line

LncBCAS1-4_1

↑lncBCAS-1_4-1 → ↑N-cadherin, ↑Vimentin, ↑ZEB1 → Epithelial-Mesenchymal Transition (EMT)

Induced expression of lncBCAS-1_4-1 disrupts the inhibitory effect of 1a,25(OH)2D3 in SKOV3 cell line (Ovarian Cancer)

[42]

Ovarian cancer

CCAT2

VD (1α,25(OH)2D3) treatment → ↓CCAT2 → dysruption binding TCF4 to MYC promoter → ↓ MYC → ↓ proliferation, migration and proliferation

By targeting CCAT2, vitamin D suppressed proliferation in ovarian cancer

[53]

Oral squamous cell carcinoma

LUCAT1

VD (1α,25(OH)2D3) treatment → ↓LUCAT1 → ERK1/2 → p- ERK1/2 → OSCC growth inhibition

VD treatment of human oral squamous cell carcinoma cell lines led to inhibition of cell proliferation by decreasing the expression of LUCAT1 which subsequently inhibited MAPK pathway activation

[44]

Coronary artery disease

MALAT1

VD supplementation increased the level of MALAT1 and decreased the level of IL22 and IL6 in coronary artery disease (CAD) patients

[46]

Vitamin D Receptor

Ovarian cancer

TOPORS-AS1

↑VDR → ↑TOPORS-AS1 → interacting with hnRNP A2B1 → ↓β-catenin

Increased expression of TOPORS-AS1 induced β-catenin degradation and suppressed the Wnt/β-catenin signalling pathway. This inhibitory effect is dependent on hnRNP A2B1.over-expression of VDR positively affects the expression of TOPORS-AS1

[43]

Myocardial ischemia

H19

Oxygen deficiency → ↑HIF → ↑H19 → ↑VDR → Cardiomyocyte apoptosis

lncRNA H19 has a key role in post-myocardial ischemia Following overexpression of HIF in hypoxic conditions, the expression of H19 and VDR increases in endothelial cells, cardiac fibroblasts, and cardiomyocytes

[61]

Ankylosing spondylitis

↑H19 → ↓ miR-22-5p or ↑ miR‐675-5p → ↑VDR → ↑ IL-17A and ↑IL-23 cytokines → ↑Inflammatory response

H19 may mediate the inflammatory process in ankylosing spondylitis (AS):as a ceRNA to compete with VDR mRNA for miR-22, or act through its derivative, miR‐675 modulating downstream Wnt/β-catenin signalling

[65]

Treatment with 1α,25(OH)₂D₃ & VDR transcript assessment

Diabetes Mellitus

H19

Through a negative feedback loop, H19 downregulates the expression of VDR via upregulation of miR‐675. EGR1 expression diminishes subsequently and inhibits H19 expression in diabetic nephropathy (DN) among patients with diabetes mellitus (DM). Treatment with 1,25D3 and EGR1 downregulated VDR at mRNA and protein levels

[64]

Glioma

Curcumin or VD (1α,25(OH)2D3) treatment → ↓ H19 → ↓ miR‐675 → ↑ VDR → ↓tumour volume (↑ apoptosis)

Curcumin and 1,25‐dihydroxyvitamin D VD (1α,25(OH)2D3) suppress H19 and miR‐675, leading to creased VDR expression with subsequent tumor volume shrinkage. VDR negatively regulates H19

[56]

Prostate cancer

AS-HSD17β2

VD (1α,25(OH)2D3) treatment & ↑VDR → ↑AS-HSD17β2 → ↓HSD17β2

AS-HSD17β2 is a direct target of VD (1α,25(OH)2D3). VD-bound VDR induced AS-HSD17β2 in HaCaT (human keratinocyte cell line) and two prostate cancer cell lines (CWR22 and PC3 cells)

[40]

Colorectal cancer

MEG3

VD (1α,25(OH)2D3) treatment or ↑VDR → ↑MEG3 → ↑ FBXW7 → ubiquitin-dependent degradation of c-MYC protein → ↓ c-MYC target genes involved in glycolysis pathway such as lactate dehydrogenases A, pyruvate kinase muscle 2 and hexokinase 2 (suppression of aerobic glycolysis in CRC cells)

Vitamin D (1,25(OH)2D3) treatment or overexpression of VDR upregulates MEG3 in human CRC cell lines. It then upregulates the FBXW7, encoding one of the subunits of ubiquitin protein ligase. This may lead to the degradation of c-MYC protein and consequent loss of expression of c-MYC target genes

[55]

VD (1α,25(OH)2D3) treatment or ↑VDR → ↑MEG3 → ↓Clusterin → inhibition of cell proliferation, migration and metastasis

MEG3 overexpression in CRC cells causes downregulation of clusterin with subsequent inhibition of cell proliferation, migration and metastasis. 1α,25-(OH)2D and vitamin D receptor (VDR) could induce expression of MEG3

[45]

H19

Through the C-Myc/Mad-1 axis, VDR signaling downregulated the expression of H19. Upregulation of H19 induce resistance to the antitumor effect of 1,25(OH)2D3 in CRC cells

[41]