Psoriasis is an autoimmune disease in which inflammation is mediated by cells and molecules of the adaptive and innate immune systems. The immune pathways which operate in psoriasis constitute exaggeration of immune tracks that occur as fundamental or stimulatory pathways in normal skin of human . Keratinocytes are major contributors in innate immunity calling up T cells to the skin, and T cells are essential in maintaining disease activity.
Inflammatory myeloid dendritic cells (DCs) secrete IL-12 and IL-23 to activate Th1 cells, Th22 cells, and IL-17–secreting T cells to release plentiful psoriatic cytokines IL-22, IL-17, TNF-α, and IFN-γ  .
The role of microRNAs in regulation of gene expression at the post-transcriptional level is deemed an essential genetic mechanism, and there were many proofs revealing that microRNAs have significant role in the pathogenesis of psoriasis .
The regulatory effect of long non coding RNAs in immune system has been a pivotal field in research toward personalized medicine. Researches on LncRNAs in immune cells detected that LncRNAs play important role in immune cells development, differentiation and activation .
The aim of this study was to examine the role of miRNA- 9 and Lnc MALAT-1 in the pathogenesis of psoriasis and their relation to disease severity. To the best of our knowledge, this is the first study to check both miRNA-9 and MALAT-1 in psoriatic patients’ lesionl and non-lesional skin as well as serum.
In the present study, the expression of miRNA-9 and lncMALAT-1 were detected by qRT-PCR in psoriatic patients and compared to controls.
Regarding miRNA-9, its serum expression was significantly increased in patients than controls, while its tissue levels were significantly decreased in patients than controls. Liang et al., deduced that microRNAs exist in blood in a stabilized format and their levels are modified in diseases .
Majd et al., revealed that microRNA-9 in increased in plasma of MS patients in relapsing phase compared to healthy controls which is an autoimmune disorder as psoriasis . O’Connell et al., studied that MicroRNA-9 participate in regulation of cell activation by many loops of feedback inhibition working at the level of NFKB1, which is a transcriptional factor greatly take part in the inflammatory response .
So, in lesional skin, one may hypothesize that the downregulation of miR-9 we detected in comparison to controls may possibly be one of the factors that contribute to the upregulation of NFKB1. Puzzlingly, Bazzoni et al., state that, the proinflammatory cytokines TNF-α, Toll-IL-1R (TIR) and IL-1β; which are all upregulated in psoriasis, causes upregulation of miR-9 levels in both PMN and monocytes .
Adding to the confusion, miRNA-9 is upregulated by NFKB1 itself via LPS and MyD88 interactions . Therefore it is justified for miRNA-9 to be upregulated in psoriasis as we detected in patients’ serum, but the fact that it was downregulated in lesional skin, needs more research and insight on this miRNA’s regulation in tissue within the context of psoriasis. Lesional, non-lesional and serum expression of long noncoding MALAT- 1 were significantly higher in patients than controls.
The increased expression of MALAT-1 in lesional skin in comparison to non-lesional skin may provide an explanation for the occurrence of plaques in these portions of the skin, that express the disease phenotype in a genetically predisposed individual, while other areas of the skin remain normal.
MALAT-1 is a long noncoding RNA whose importance in immune regulation stays mostly obscure. Several researches have revealed that LncRNAs can be used as biomarkers for diagnosis and prognosis of diseases. Lately, abnormal expression of LncRNAs has been detected in rheumatoid arthritis and many autoimmune disorders .
In the present study, MALAT-1 was significantly increased in psoriatic patients, lesional, non lesional and serum samples compared to controls. Dysregulation of MALAT-1 appeared to be NF-ƘB- dependent. NF-ƘB is a major transcription factor which is important for promoter activity of MALAT-1 .
Furthermore, Puthanveetil et al., displayed that hyperglycemia initiates an inflammatory response cascade through MALAT-1 mediated up-regulation of serum amyloid antigen, thus inducing the release of inflammatory markers TNF-α and IL-6, both of which are major regulators in pathogenesis of psoriasis . So, it seems that MALAT-1 carries the potential of upregulation of key players in psoriasis development including NF-ƘB, IL-6 and TNF-α, although the exact mechanism of the latter 2 cytokines needs verification.
A good example of abnormal expression of MALAT-1 in autoimmune disease is reported by Yang et al., who showed that MALAT-1 was upregulated in PBMCs from autoimmune disease (SLE) patients compared to that in healthy controls, and the major regulatory role of MALAT-1 in the pathogenesis of systemic lupus via SIRT1signaling pathway . Rasheed et al., detected dysregulation of SIRT1 in psoriasis patients in comparison to healthy controls  and Yang et al., reported the role of MALAT-1 in regulation of SIRT1 signaling pathway .
In the present study, results showed that lesion level of miRNA-9 and MALAT-1 was higher in females than males. Our result was confirmed by Zandman et al., and Greer et al., who detected that various stimuli may differentially impact females and males, making the higher potential of autoimmune diseases among females .
Alonso and Hernan revealed that for epigenetic modifications to explain sexual dimorphism in autoimmunity, it is important to assume that epigenetic factors are more commonly occurred in one gender than in the other, or that individuals of one sex are more susceptible than the other . While, in view of the higher incidence of some autoimmune diseases among females, but not males, over the last 100 years, and the main social changes that mostly influenced females over that time, it is an appealing supposition.
Moreover, the significant positive correlation between non- lesion miRNA-9 and both extend of disease and BPSA affected by psoriasis, suggests an important relationship between this miRNA and the disease initiation and activity, and may encourage further investigations to explore the possibility of using this miRNA as one of the markers of psoriasis severity.
Interestingly, serum MALAT-1 expression was positively correlated with disease extension, PASI score and BPSS among cases, which indicated that the increase in these variables was associated with increase in serum level of MALAT-1. Such observations may suggest a direct participation of MALAT-1 in the development and severity of psoriasis.
In the current study, a significant positive correlation between serum level of MALAT-1 and each of lesion , non-lesion, and serum level of MiRNA-9 among cases with p-value <0.05, which indicated that the increase in serum level of MALAT-1 was associated with increase in lesion, non-lesion and serum level of micro RNA- 9.
These results are opposing the result of Leucci et al., who reported that miRNA-9 overexpression resulted in a significant downregulation of MALAT-1 both in the cytoplasm and the nucleus of L428 Hodgkin lymphoma cells . Psoriasis and lymphoma are 2 diverse disorders with very different pathogenesis and immune dysregulations. The relation of miRNA-9 with MALAT-1 cannot be simply restricted to a dual interaction when a vast number of cytokines involved in psoriasis are dysregulated; e.g. NFKB, TIR-IL1 and TNF, and are shown to be direct regulators of miRNA-9 and or MALAT-1.