Zaixing Wang

RETRACTED: Construction of circular miRNA sponges targeting miR-21 or miR-221 and demonstration of their excellent anticancer effects on malignant melanoma cells

microRNA sponges antagonizing the oncogenic microRNAs are potential candidates for RNA-based cancer therapies. Although the constructed sponges so far are to some extent suitable for biological experiments, they can only express at relative low levels in cells, because they are sensitive to microRNA-mediated activation of deadenylation and subsequent exonucleolytic degradation. Since circular RNA molecules are resistant to exonuclease degradation, we report the production of circular microRNA sponges against miR-21 or miR-221 in cell lines using the self-splicing permuted intron-exon sequences derived from T4 bacteriophage gene td. The circularized microRNA sponges withstand enzymatic degradation and are completely resistant to microRNA-mediated degradation. They are more effective than typical linear microRNA sponges and microRNA inhibitors in derepressing microRNA targets. They also display superior anti-cancer activities compared to the linear sponges in malignant melanoma cell lines. We have provided an alternative method for circular microRNA sponge production and malignant melanoma treatment.

Antiproliferation and apoptosis induction of paeonol in human esophageal cancer cell lines

The incidence of esophageal cancer (EC), especially adenocarcinoma, has increased tremendously in Western countries and the prognosis of EC remains poor. Paeonol (Pae), a phenolic component from the root bark of Paeonia moutan, possesses antitumor effects in vitro and in vivo. The present study showed that Pae had an antiproliferative effect on the two human EC cell lines (SEG-1 and Eca-109), with different sensitivities to Pae. Acridine orange staining and flow cytometry assays showed that Pae induced apoptosis on the two cell lines. Further analyses indicated that Pae resulted in a cell cycle arrest at S-phase. Immunohistochemical staining showed the expression of Bcl-2 was decreased and that of Bax was increased in treatment groups, with the ratio of Bcl-2/Bax decreased correspondingly. The results show that Pae shows growth inhibitory and apoptosis induction property and may be a promising agent for the EC treatment.

Association of HLA‐DQA1 and DQB1 genes with vitiligo in Chinese Hans

Background  Vitiligo is an acquired depigmentary disorder of the skin and hair which results from selective destruction of melanocytes. Serological typing and genotyping of human leukocyte antigen (HLA) have shown discrepancies in HLA associations with vitiligo in different ethnic populations.

Synergistic effect of paeonol and cisplatin on oesophageal cancer cell lines

BACKGROUND/AIM Paeonol, a phenolic component from the root bark of Paeonia moutan, has shown great promise in antitumour activities in our previous studies. The present study was designed to investigate whether paeonol has synergistic effect with cisplatin on the growth-inhibitory of human oesophageal cancer cell lines and the possible mechanism. METHODS Cell viability was measured by MTT assay. Drug-drug interactions were analysed by the coefficient of drug interaction. Apoptosis was detected by acridine orange fluorescence staining and flow cytometry assay. Bcl-2, Bax and caspase-3 expression was assayed by immunohistochemical staining. RESULTS A synergistic inhibitory effect on viability of the two cell lines was observed after combination of paeonol with various concentrations of cisplatin. Further study showed the combination induced greater apoptosis than the groups treated with paeonol or cisplatin alone. The expression of Bcl-2 was decreased and that of Bax was increased in treatment groups, especially in the combination group, with the ratio of Bcl-2/Bax decreased correspondingly. And the combination also resulted in greater activation of caspase-3 than did either agent alone. CONCLUSIONS Paeonol, in combination with cisplatin, had a significantly synergistic growth-inhibitory effect on oesophageal cell line, which may be related to apoptosis induction.

HLA-DQA1 and DQB1 alleles are associated with genetic susceptibility to psoriasis vulgaris in Chinese Han.

Background  Psoriasis vulgaris is a chronic skin disorder characterized by infiltration of inflammatory elements, keratinocyte hyperproliferation and altered differentiation. Although the pathogenesis of psoriasis is not fully understood, there is solid evidence of a susceptibility locus in the human leukocyte antigen (HLA) region.

Exome sequencing identifies SLC17A9 pathogenic gene in two Chinese pedigrees with disseminated superficial actinic porokeratosis

Background Disseminated superficial actinic porokeratosis (DSAP) is a rare autosomal dominant genodermatosis characterised by annular lesions that has an atrophic centre and a prominent peripheral ridge distributed on sun exposed area. It exhibits high heterogeneity, and five linkage loci have been reported. The mevalonate kinase (MVK) gene located on 12q24 has been confirmed as one of the disease-causing genes. But, the pathogenesis of a large part of DSAP remains unclear so far. Methods The recruited with DSAP carried no MVK coding mutations. Exome sequencing was performed in two affected and one unaffected individual in Family 1. Cosegregation of the candidate variants was tested in other family members. Sanger sequencing in 33 individuals with familial DSAP and 19 sporadic DSAP individuals was performed for validating the causative gene. Results An average of 1.35×105 variants were generated from exome data and 133 novel NS/SS/indels were identified as being shared by two affected individuals but absent in the unaffected individual. After functional prediction, 25 possible deleterious variants were identified. In Family 1, a missense variant c.932G>A (p.Arg311Gln) in exon 10 of SLC17A9 was observed in cosegregation with the phenotype; this amino acid substitution was located in a highly conserved major facilitator superfamily (MFS) domain in multiple mammalian. One additional missense variant c.25C>T (p.Arg9Cys) in exon 2 of SLC17A9 was found in Family 2. Conclusions The result identified SLC17A9 as another pathogenic gene for DSAP, which suggests a correlation between the aberrant vesicular nucleotide transporter and the pathogenesis of DSAP.

Association of HLA class I alleles with keloids in Chinese Han individuals.

Keloids are benign fibroproliferative dermal tumors of unknown etiology. Some studies have suggested that human HLA status might potentiate development of keloids phenotype. No report has been published about HLA class I alleles associated with keloids in Chinese Han individuals. To investigate the etiology of keloids, the polymerase chain reaction-sequence-specific primer (PCR-SSP) method was used to analyze the distribution of HLA class I alleles in 192 patients with keloids and 252 healthy controls in a Chinese Han population. The frequencies of HLA-A*03 (6.77% vs 0%, p(c) < 10(-7)), A*25 (10.16% vs 4.56%, p(c) = 0.0111), B*07 (7.81% vs 2.58%, p(c) = 0.0080), and Cw*0802 (19.79% vs 10.32%, p(c) = 0.0004) were significantly increased in keloid patients, whereas the frequency of HLA-A*01 (18.75% vs 38.10%, p(c) < 10(-7)) was highly decreased, compared with that in healthy controls. The A*03-B*07, A*25-B*07, A*03-Cw*0802, A*25-Cw*0802, and B*07-Cw*0802 were found as high-risk haplotypes in developing keloids in this study. No extended haplotype was found to be significantly related to keloids. Through stratified analysis, the association of subgroups (single site/multiple site, severity, and family history) of keloid patients with specific HLA alleles was identified. Our data suggest these alleles may be keloids susceptibility genes or may be in close linkage with the susceptibility genes.

The study of the participation of basement membrane zone antibodies in the formation of the lupus band in systemic lupus erythematosus

Background  The lupus band test (LBT) is an important auxiliary method in the diagnosis of systemic lupus erythematosus (SLE), but the mechanism of its formation is still unknown. There are many kinds of autoantibodies, such as basement membrane zone autoantibodies (BMZ‐Abs), in patients with SLE.

A genetic coding variant rs72474224 in GJB2 is associated with clinical features of psoriasis vulgaris in a Chinese Han population

Our recent targeted sequencing study identified a missense single-nucleotide polymorphism rs72474224 (c.324C>T) in GJB2. To investigate the correlation between rs72474224 (c.324C>T) and subphenotypes of psoriasis, genotype data for rs72474224 (c.324C>T, p.Val37Ile) was analyzed in 9946 cases and 9906 controls. The additive model provided the best fit for rs72474224 (P = 7.34 × 10(-9)). The genotypic and allelic frequency distributions were associated with plaque psoriasis in case-only (Pgenotype = 2.67 × 10(-3), Pallele = 6.22 × 10(-4)) and subphenotype-control (Pgenotype = 1.58 × 10(-11), Pallele = 8.16 × 10(-12)) analyses. No other significant difference was found in case-only analyses. Rs72474224 in GJB2 is preferentially associated with plaque psoriasis in Chinese population and might contribute to the complexity of psoriasis clinical features.

A novel missense mutation of the ATP2A2 gene in a Chinese family with Darier’s disease

Darier’s disease (DD) is an autosomal dominant skin disorder that is characterized by multiple keratotic papules, focal loss of adhesion and abnormal keratinization. Mutations in the ATP2A2 gene encoding sarco/endoplasmic reticulum calcium pumping ATPase type 2 have been identified as the molecular basis of DD. We report here a three-generation family with DD, and examined ATP2A2 gene mutations in this family by direct sequencing. A novel missense mutation A→G was identified in exon 12, nucleotide 1704, which leads to the substitution of lysine by arginine at codon 514 (K514R). This study contributes to the database on ATP2A2 in DD, and further illustrates the extensive diversity of mutational events that lead to the different phenotypes of DD.