LIM Homeobox Domain 2 Is Required for Corneal Epithelial Homeostasis

Sartaj, Rachel; Chee, Ru Ik; Yang, Jing; Park, Wan; Liu, Aihong; Guaiquil, Victor H.; Fuchs, Elaine; Rosenblatt, Mark I.

doi:10.1002/stem.2257

Cited by 5 publications

(4 citation statements)

References 34 publications

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“…In the current study, miR-506 was suggested to be involved in inhibiting the activation of the Wnt/β-catenin signaling pathway by down-regulating LHX4, by means of which the EMT-related signals were inhibited. It has been suggested that LHX2 plays a pivotal role in various epithelial-mesenchymal interactions [49]. Multiple signaling pathways, including the nuclear factor kappa B, EGFR, Wnt and transforming growth factor-β (TGF-β) signaling pathways, are involved in the regulation of EMT and LNM [50–53].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: MicroRNA-506 inhibits tumor growth and metastasis in nasopharyngeal carcinoma through the inactivation of the Wnt/β-catenin signaling pathway by down-regulating LHX2

Liang

Zheng

Wang

et al. 2019

J Exp Clin Cancer Res

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Background Epithelial-mesenchymal transition (EMT)-associated proteins play key roles in cancer progression and metastasis with the involvement of microRNAs (miRNAs). This study aims to assess the role of miR-506 working in tandem with LIM Homeobox 2 (LHX2) in EMT and metastasis through the Wnt/β-catenin signaling pathway in nasopharyngeal carcinoma (NPC). Methods Differentially expressed genes associated with NPC were screened using microarray analyses, from which LHX2 was identified. Next, the potential relationship between miR-506 and LHX2 was analyzed. In order to explore the effect of miR-506 or LHX2 on NPC cell proliferation, migration, invasion and apoptosis, serials of mimics, inhibitors or siRNA against LHX2 were transfected into NPC cells. Then, the expression patterns of LHX2, Wnt1, β-catenin, E-cadherin, Vimentin, TCF4 and Twist were determined to assess the influence of miR-506 or LHX2 on EMT as well as the relationship between the Wnt/β-catenin signaling pathway and TCF4. The tumorigenicity and lymph node metastasis (LNM) in xenograft tumors of nude mice were observed. Results The has-miR-506-3p was identified as the down-regulated gene in NPC based on the microarray data while LHX2 was negatively regulated by miR-506. Over-expression of miR-506 or silencing of LHK2 inhibited NPC cell proliferation, migration, invasion, tumorigenicity and LNM but promoted apoptosis indicated by decreased Wnt1, β-catenin, Vimentin, TCF4 and Twist expressions along with increased E-cadherin expressions. Conclusions miR-506 inhibits tumor growth and metastasis in NPC via inhibition of Wnt/β-catenin signaling by down-regulating LHX2, accompanied by decreased TCF4. Taken together, miR-506 targeted-inhibition LHX2 presents a promising therapeutic strategy for the treatment of NPC. Trial registration ChiCTR1800018889 . Registered 15 October 2018. Electronic supplementary material The online version of this article (10.1186/s13046-019-1023-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: MicroRNA-506 inhibits tumor growth and metastasis in nasopharyngeal carcinoma through the inactivation of the Wnt/β-catenin signaling pathway by down-regulating LHX2

Liang

Zheng

Wang

et al. 2019

J Exp Clin Cancer Res

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“…These results suggest that both central and limbal epithelial cells are responsive to ocular surface injury, possibly exerting different roles in the process of wound healing. After scraping the epithelium, the cornea healed fully within 72 hours, as reported earlier [38], but we could not detect a change in the Bmi1 + cell progeny patterning nor the amount or distribution of the Ki67+ cells. Instead, we saw that the epithelium was thin 18 hours after injury, which corresponds to the active period of healing.…”

Section: Discussionsupporting

confidence: 80%

Bmi1+ Progenitor Cell Dynamics in Murine Cornea During Homeostasis and Wound Healing

et al. 2018

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The outermost layer of the eye, the cornea, is renewed continuously throughout life. Stem cells of the corneal epithelium reside in the limbus at the corneal periphery and ensure homeostasis of the central epithelium. However, in young mice, homeostasis relies on cells located in the basal layer of the central corneal epithelium. Here, we first studied corneal growth during the transition from newborn to adult and assessed Keratin 19 (Krt19) expression as a hallmark of corneal maturation. Next, we set out to identify a novel marker of murine corneal epithelial progenitor cells before, during and after maturation, and we found that Bmi1 is expressed in the basal epithelium of the central cornea and limbus. Furthermore, we demonstrated that Bmi1+ cells participated in tissue replenishment in the central cornea. These Bmi1+ cells did not maintain homeostasis of the cornea for more than 3 months, reflecting their status as progenitor rather than stem cells. Finally, after injury, Bmi1+ cells fueled homeostatic maintenance, whereas wound closure occurred via epithelial reorganization. Stem Cells 2018;36:562-573.

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“…As LESCs are induced to proliferate in order to repair large wounds ( Lehrer et al., 1998 ), the poor wound healing response suggests LESCs are deficient in Lrig1 −/− mice. Similar evidence suggests that the abnormal corneal epithelial morphology, implying impaired corneal homeostasis, which was seen in some K14-Cre ; Lhx2 fl/fl mice also involved a LESC deficiency ( Sartaj et al., 2016 ). After successive corneal epithelial debridements, wound healing was incomplete in K14-Cre ; Lhx2 fl/fl mice and their corneal epithelium contained goblet cells and K15-positive cells.…”

Section: Introductionmentioning

confidence: 68%

Abnormal corneal epithelial maintenance in mice heterozygous for the micropinna microphthalmia mutation Mp

Douvaras

Dora

Mort

et al. 2016

Experimental Eye Research

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We investigated the corneal morphology of adult Mp/+ mice, which are heterozygous for the micropinna microphthalmia mutation, and identified several abnormalities, which implied that corneal epithelial maintenance was abnormal. The Mp/+ corneal epithelium was thin, loosely packed and contained goblet cells in older mice. Evidence also suggested that the barrier function was compromised. However, there was no major effect on corneal epithelial cell turnover and mosaic patterns of radial stripes indicated that radial cell movement was normal. Limbal blood vessels formed an abnormally wide limbal vasculature ring, K19-positive cells were distributed more widely than normal and K12 was weakly expressed in the peripheral cornea. This raises the possibilities that the limbal-corneal boundary was poorly defined or the limbus was wider than normal. BrdU label-retaining cell numbers and quantitative clonal analysis suggested that limbal epithelial stem cell numbers were not depleted and might be higher than normal. However, as corneal epithelial homeostasis was abnormal, it is possible that Mp/+ stem cell function was impaired. It has been shown recently that the Mp mutation involves a chromosome 18 inversion that disrupts the Fbn2 and Isoc1 genes and produces an abnormal, truncated fibrillin-2MP protein. This abnormal protein accumulates in the endoplasmic reticulum (ER) of cells that normally express Fbn2 and causes ER stress. It was also shown that Fbn2 is expressed in the corneal stroma but not the corneal epithelium, suggesting that the presence of truncated fibrillin-2MP protein in the corneal stroma disrupts corneal epithelial homeostasis in Mp/+ mice.

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LIM Homeobox Domain 2 Is Required for Corneal Epithelial Homeostasis

Cited by 5 publications

References 34 publications

RETRACTED ARTICLE: MicroRNA-506 inhibits tumor growth and metastasis in nasopharyngeal carcinoma through the inactivation of the Wnt/β-catenin signaling pathway by down-regulating LHX2

RETRACTED ARTICLE: MicroRNA-506 inhibits tumor growth and metastasis in nasopharyngeal carcinoma through the inactivation of the Wnt/β-catenin signaling pathway by down-regulating LHX2

Bmi1+ Progenitor Cell Dynamics in Murine Cornea During Homeostasis and Wound Healing

Abnormal corneal epithelial maintenance in mice heterozygous for the micropinna microphthalmia mutation Mp

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