WAKMAR2, a Long Noncoding RNA Downregulated in Human Chronic Wounds, Modulates Keratinocyte Motility and Production of Inflammatory Chemokines

Herter, Eva K.; Li, Dongqing; Toma, Maria Alexandra; Vij, Manika; Li, Xi; Visscher, Dani; Wang, Aoxue; Chu, Tongbin; Sommar, Pehr; Blomqvist, Lennart; Berglund, David; Ståhle, Mona; Wikström, Jakob D.; Landén, Ning Xu

doi:10.1016/j.jid.2018.11.033

Cited by 44 publications

(50 citation statements)

References 62 publications

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“…According to our screening criteria, WAKMAR2 was selected to enter the follow-up study. The original name of WAKMAR2 is LOC100130476, its genomic locus is very special, its transcription direction is antisense, and there is an overlapping region with the TNFAIP3 gene body and promoter part [20,21]. The expression of WAKMAR2 and TNFAIP3 has a strong correlation in various tumor types.…”

Section: Discussionmentioning

confidence: 99%

WAKMAR2, a Prognosis-related Enhancer RNA in Gastric Cancer

Zhang¹,

Yan²,

Ning³

et al. 2020

Preprint

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Purpose An increasing number of long non-coding RNAs (lncRNAs) are thought to be associated with gastric cancer (GC). A lncRNA subclass that promotes enhancer function is called enhancer RNA (eRNA). We aimed to identify an eRNA that can predict GC prognosis and response to immune checkpoint inhibitors (ICIs).Methods Kaplan–Meier survival analysis was utilized to screen eRNA which can predict the prognosis of GC (P <0.05). The method of Spearman correlation analysis was employed in the filtration of target genes related to eRNA (r> 0.4, P <0.001). According to the median of WAKMAR2 expression, the patients were subdivided into low expression group and high expression group. Subsequently, differences of immune checkpoint-related genes and immune cell infiltration between the two groups were further explored. Furthermore, we analyzed the correlation of WAKMAR2 with tumor mutation burden (TMB) and microsatellite instability (MSI) in GC and other types of cancer.Results WAKMAR2 and its target gene TNFAIP3 entered the subsequent analysis. Patients with high-WAKMAR2 expression had a favorable prognosis compared to patients with low-WAKMAR2 expression (P = 0.048). Immune checkpoint-related genes (PD-L1, CTLA4, PDCD1, LAG3) in the WAKMAR2 high-expression group were also highly expressed, except for B7-H3. In addition, infiltration levels of B cells naive, T cells CD8, T cells CD4 memory activated, as well as Macrophages M1 in high-WAKMAR2 group were greater than in low-WAKMAR2 group. Last, the expression of WAKMAR2 in GC was significantly correlated with TMB and MSI.Conclusion WAKMAR2, a new eRNA, is a promising biomarker that can be used to predict the overall survival (OS) of GC patients, and WAKMAR2 expression can be utilized to identify ICB responders in GC, providing new insights for immunotherapy strategies.

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Section: Discussionmentioning

confidence: 99%

WAKMAR2, a Prognosis-related Enhancer RNA in Gastric Cancer

Zhang¹,

Yan²,

Ning³

et al. 2020

Preprint

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“…15 Full keratinocyte coverage (i.e., epithelization) is the defining clinical criteria of a closed wound. 16 Li et al identified novel roles for two lncRNAs-LOC105372576 (renamed WAKMAR1 [wound and keratinocyte migration-associated lncRNA 1]), 17 and LOC100130476 (renamed (WAKMAR2 [wound and keratinocyte migration-associated lncRNA 2]) 18 -that both increase keratinocyte migration in wound F I G U R E 1 Role of long noncoding RNA (lncRNA) in endothelial cell (EV)-derived bioactivity. (a) Expression levels of the indicated lncRNAs were assessed by qPCR in EVs from human umbilical vein endothelial cells (HUVECs) cultured in the presence versus absence of 100 mM ethanol (EtOH) for 24 hr (n = 3; *p < .05).…”

Section: Integumentary Systemmentioning

confidence: 99%

Therapeutic potential of extracellular vesicle‐associated long noncoding RNA

Born

Harmon

Jay

2020

Bioengineering & Transla Med

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Both extracellular vesicles (EVs) and long noncoding RNAs (lncRNAs) have been increasingly investigated as biomarkers, pathophysiological mediators, and potential therapeutics. While these two entities have often been studied separately, there are increasing reports of EV-associated lncRNA activity in processes such as oncogenesis as well as tissue repair and regeneration. Given the powerful nature and emerging translational impact of other noncoding RNAs such as microRNA (miRNA) and small interfering RNA, lncRNA therapeutics may represent a new frontier. While EVs are natural vehicles that transport and protect lncRNAs physiologically, they can also be engineered for enhanced cargo loading and therapeutic properties. In this review, we will summarize the activity of lncRNAs relevant to both tissue repair and cancer treatment and discuss the role of EVs in enabling the potential of lncRNA therapeutics. K E Y W O R D S exosomes, extracellular vesicles, lncRNA, microparticles, microvesicles lncRNAs play diverse regulatory roles in normal physiological processes. Thus, delivery of lncRNAs via EVs may help in the treatment Abbreviations: CRCs, colorectal carcinoma cells; EVs, extracellular vesicles; hAD-MSCs, human adipose-derived mesenchymal stem cells; HCAECs, human coronary artery endothelial cells; HCC, hepatocellular carcinoma cell; HDFs, human dermal fibroblasts; HDMECs, human dermal microvascular endothelial cells; lncRNA, long noncoding RNA; miRNA, microRNA; SCCs, squamous carcinoma cells.

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“…Wound and keratinocyte migration-associated lncRNA 1 and 2 (WAKMAR1 and WAKMAR2) are two recently identified lncRNAs, which play an important role in cutaneous wound repair [90,91]. Expression of WAKMAR1 is highly upregulated in keratinocytes during wound repair and its expression stimulates keratinocyte migration and wound re-epithelization [90].…”

Section: Deregulation Of Lncrnas Is Becoming Evident In Cscc Progressmentioning

confidence: 99%

“…Expression of WAKMAR1 is highly upregulated in keratinocytes during wound repair and its expression stimulates keratinocyte migration and wound re-epithelization [90]. Expression of both WAKMAR1 and WAKMAR2 is induced by TGF-β and downregulation of their expression inhibits migration of keratinocytes, resulting in delayed wound re-epithelization [90,91]. Accordingly, the expression of both WAKMAR1 and WAKMAR2 is reduced in keratinocytes in the edge of chronic wounds in vivo [90,91].…”

Section: Deregulation Of Lncrnas Is Becoming Evident In Cscc Progressmentioning

confidence: 99%

“…Expression of both WAKMAR1 and WAKMAR2 is induced by TGF-β and downregulation of their expression inhibits migration of keratinocytes, resulting in delayed wound re-epithelization [90,91]. Accordingly, the expression of both WAKMAR1 and WAKMAR2 is reduced in keratinocytes in the edge of chronic wounds in vivo [90,91]. Moreover, upregulation of WAKMAR2 expression inhibits production of inflammatory chemokines by keratinocytes, and this way promotes wound healing [91].…”

Section: Deregulation Of Lncrnas Is Becoming Evident In Cscc Progressmentioning

confidence: 99%

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Long non-coding RNAs in cutaneous biology and keratinocyte carcinomas

Piipponen

Nissinen

Kähäri

2020

Cell. Mol. Life Sci.

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Long non-coding RNAs (lncRNAs) are a largely uncharacterized group of non-coding RNAs with diverse regulatory roles in various biological processes. Recent observations have elucidated the functional roles of lncRNAs in cutaneous biology, e.g. in proliferation and differentiation of epidermal keratinocytes and in cutaneous wound repair. Furthermore, the role of lncRNAs in keratinocyte-derived skin cancers is emerging, especially in cutaneous squamous cell carcinoma (cSCC), which presents a significant burden to health care services worldwide and causes high mortality as metastatic disease. Elucidation of the functions of keratinocyte-specific lncRNAs will improve understanding of the molecular pathogenesis of epidermal disorders and skin cancers and can be exploited in development of new diagnostic and therapeutic applications for keratinocyte carcinomas. In this review, we summarize the current evidence of functionally important lncRNAs in cutaneous biology and in keratinocyte carcinomas.

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WAKMAR2, a Long Noncoding RNA Downregulated in Human Chronic Wounds, Modulates Keratinocyte Motility and Production of Inflammatory Chemokines

Cited by 44 publications

References 62 publications

WAKMAR2, a Prognosis-related Enhancer RNA in Gastric Cancer

WAKMAR2, a Prognosis-related Enhancer RNA in Gastric Cancer

Therapeutic potential of extracellular vesicle‐associated long noncoding RNA

Long non-coding RNAs in cutaneous biology and keratinocyte carcinomas

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