Regulation of melanoma malignancy by the RP11-705C15.3/miR-145-5p/NRAS/MAPK signaling axis.

Melanoma is a common lethal skin cancer. Dissecting molecular mechanisms driving the malignancy of melanoma may uncover potential therapeutic targets. We previously identified miR-145-5p as an important tumor-suppressive microRNA in melanoma. Here, we further investigated the roles of long non-coding RNAs (lncRNAs) in melanoma. We identified RP11-705C15.3, a regulator of miR-145-5p, as an oncogenic lncRNA in melanoma. RP11-705C15.3 competitively bound miR-145-5p, relieved the repressive roles of miR-145-5p on its target NRAS, upregulated NRAS expression, and activated MAPK signaling. In vitro functional assays revealed that ectopic expression of RP11-705C15.3 promoted melanoma cell proliferation, inhibited apoptosis, and promoted migration and invasion. Silencing of RP11-705C15.3 repressed melanoma cell proliferation, induced apoptosis, and repressed migration and invasion. Notably, the roles of RP11-705C15.3 in melanoma cell proliferation, apoptosis, migration and invasion are reversed by miR-145-5p overexpression. In vivo functional assays revealed that RP11-705C15.3 promoted melanoma tumor growth and metastasis, which were also reversed by miR-145-5p overexpression. Furthermore, we investigated the expression of RP11-705C15.3 in clinical melanoma tissues and found that RP11-705C15.3 was increased in melanoma tissues. High expression of RP11-705C15.3 was positively correlated with thickness, ulceration, metastasis, and inferior overall survival. Taken together, our findings suggest RP11-705C15.3 as a novel oncogene in melanoma, and highlight that the RP11-705C15.3/miR-145-5p/NRAS/MAPK signaling axis may be potential therapeutic targets for melanoma.

FUT8-AS1 Inhibits the Malignancy of Melanoma Through Promoting miR-145-5p Biogenesis and Suppressing NRAS/MAPK Signaling.

Melanoma is the major lethal skin malignancy. However, the critical molecular drivers governing melanoma progression and prognosis are still not clear. By analyzing The Cancer Genome Atlas (TCGA) data, we identified FUT8-AS1 as a prognosis-related long non-coding RNA (lncRNA) in melanoma. We further confirmed that FUT8-AS1 is downregulated in melanoma. Reduced expression of FUT8-AS1 is correlated with aggressive clinical factors and inferior overall survival. Using in vitro functional assays, our findings demonstrated that ectopic expression of FUT8-AS1 represses melanoma cell proliferation, migration, and invasion. FUT8-AS1 silencing promotes melanoma cell proliferation, migration, and invasion. Furthermore, in vivo functional assays demonstrated that FUT8-AS1 represses melanoma growth and metastasis. Mechanistically, FUT8-AS1 was found to bind NF90, repress the interaction between NF90 and primary miR-145 (pri-miR-145), relieve the repressive roles of NF90 on mature miR-145-5p biogenesis, and thus promote miR-145-5p biogenesis and upregulate mature miR-145-5p level. The expression of FUT8-AS1 is positively correlated with miR-145-5p in melanoma tissues. Via upregulating miR-145-5p, FUT8-AS1 reduces the expression of NRAS, a target of miR-145-5. FUT8-AS1 further represses MAPK signaling via downregulating NRAS. Functional rescue assays demonstrated that inhibition of miR-145-5p reverses the tumor suppressive roles of FUT8-AS1 in melanoma. The oncogenic roles of FUT8-AS1 silencing are also blocked by MAPK signaling inhibitor MEK162. In conclusion, these findings demonstrate that FUT8-AS1 exerts tumor suppressive roles in melanoma via regulating NF90/miR-145-5p/NRAS/MAPK signaling axis. Targeting FUT8-AS1 and its downstream molecular signaling axis represent promising therapeutic strategies for melanoma.

Genotyping of Soybean Cultivars With Medium-Density Array Reveals the Population Structure and QTNs Underlying Maturity and Seed Traits.

Soybean was domesticated about 5,000 to 6,000 years ago in China. Although genotyping technologies such as genotyping by sequencing (GBS) and high-density array are available, it is convenient and economical to genotype cultivars or populations using medium-density SNP array in genetic study as well as in molecular breeding. In this study, 235 cultivars, collected from China, Japan, USA, Canada and some other countries, were genotyped using SoySNP8k iSelect BeadChip with 7,189 single nucleotide polymorphisms (SNPs). In total, 4,471 polymorphic SNP markers were used to analyze population structure and perform genome-wide association study (GWAS). The most likely K value was 7, indicating this population can be divided into 7 subpopulations, which is well in accordance with the geographic origins of cultivars or accession studied. The LD decay rate was estimated at 184 kb, where r2 dropped to half of its maximum value (0.205). GWAS using FarmCPU detected a stable quantitative trait nucleotide (QTN) for hilum color and seed color, which is consistent with the known loci or genes. Although no universal QTNs for flowering time and maturity were identified across all environments, a total of 30 consistent QTNs were detected for flowering time (R1) or maturity (R7 and R8) on 16 chromosomes, most of them were corresponding to known E1 to E4 genes or QTL region reported in SoyBase (soybase.org). Of 16 consistent QTNs for protein and oil contents, 11 QTNs were detected having antagonistic effects on protein and oil content, while 4 QTNs soly for oil content, and one QTN soly for protein content. The information gained in this study demonstrated that the usefulness of the medium-density SNP array in genotyping for genetic study and molecular breeding.

[Occurrence characteristics and molecular genetic basis of pod shattering in soybean].

Pod shattering is a natural property of wild soybean (Glycine soja) for propagation and also a major cause of yield loss in cultivated soybean (Glycine max L. Merr). Thus, studies on occurrence characteristics and molecular genetic basis of pod shattering in soybean can provide insights into both molecular mechanisms and potential application in legume crop improvement. In this review, we summarize the occurrence features and phenotypic identification methods of pod shattering based on analysis of the cellular microstructure of shattering-resistant soybean pod. We also introduced the identification and breeding of shattering-resistant germplasms, the progress of molecular genetic studies on shattering-resistant phenotype in soybean as well as perspectives on future studies of pod-shattering trait and application in crop improvement.

Epidemiology of bedside stove burns in a retrospective cohort of 5089 pediatric patients.

OBJECTIVE: To retrospectively analyze the epidemiological characteristics of pediatric bedside stove burns (PBSB) in China and to explore prevention and control measures. METHODS: Data on pediatric burns from three hospitals located in the epidemic area were collected from January 1996 to December 2010 and were divided into the PBSB group and the control group. The epidemiological characteristics and related information for each patient were analyzed. RESULTS: A total of 16,595 pediatric burns were found, including 5089 PBSB and 11,506 other types of burns. The two groups differed significantly in terms of age, gender, body parts burned, degree of burn, delay of hospitalization, and treatment measures (Ps all<0.05). Risk factors for PBSB included being younger than 3 years old, living in a rural area, low literacy level of guardians, not receiving health education, and lack of a protective fence protection (Ps all<0.05). Furthermore, meal time and winter and spring seasons were high risk periods for PBSB. CONCLUSION: The risk factors for PBSB include age, region, time of occurrence, and literacy level of guardians. Health education and installation of a protective fence between the stove and the bed could reduce the incidence of PBSB.

Three-dimensional digitalized virtual planning for retrograde sural neurovascular island flaps: a comparative study.

BACKGROUND: The purpose of this study was to explore the effectiveness and safety of three-dimensional (3D) digitalized planning for the sural neurovascular island flap in repair of soft tissue defects in the ankle and foot. METHODS: This study included 40 patients with soft tissue defects of the ankle and foot who underwent soft tissue reconstruction between October 2008 and June 2012. The patients were randomly assigned into two groups: 3D-reconstruction group (Group A, n=20) and control group (Group B, n=20). Three-dimensional, digitalized virtual planning was performed in the patients in Group A, who underwent computed topographic angiography. The survival rate, operation time, and surgical accuracy were compared between the two groups. RESULTS: All flaps in Group A survived and the recipient site primarily healed, but 4 flaps in Group B had marginal necrosis after the operation. During the 6-12 month follow-up period, all flaps in Group A had good skin quality. In Group B, hard scarring and mild contracture occurred in 4 cases, and the patients experienced pain when walking. The survival rate of the flap in Group A (100%) was significantly higher than in Group B (70%). The operation time in Group A was significantly less than in Group B. The surgical accuracy in Group A was significantly better than in Group B. CONCLUSION: The preoperative use of 3D digitalized virtual planning for the sural neurovascular island flap improves the surgical accuracy, decreases the operation time, and increases the survival rate of the flap. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic III.

[Analysis of clinical data of 16 595 pediatric burn patients during fifteen years].

OBJECTIVE: To analyze the epidemiological characteristics of pediatric burn in the midwest region of Inner Mongolia and the related areas, and to provide reference for seeking pertinent measures of prevention and treatment. METHODS: Medical records of patients hospitalized in the 253rd Hospital of PLA, the 322nd Hospital of PLA, and the Inner Mongolia Autonomous Region Hospital from January 1996 to December 2010 were collected. Patients were divided into pediatric burn group with specific reason (group SF, with scald resulted from construction defect of Guo-lian-kang--a heatable brick bed linked to a cooking pot), and burn control group with other causes (group C) according to the main injury cause. Clinical data of patients in both groups, including general condition, family background, occurrence regularity, and outcome, were analyzed. The epidemiological trend of variation before and after taking preventive measures (1996 to 2001 and 2002 to 2010) was compared. Data were processed with chi-square test and rank sum test. RESULTS: (1) General condition: out of 16 595 pediatric burn patients, 15 816 cases (95.3%) suffered scald due to liquids with high temperature, and 779 cases (4.7%) suffered burns due to other causes. Patients in group SF (scald due to specific cause--Guo-lian-kang) accounted for 32.2% (5089/15 816) of the total suffered scald by liquids with high temperature, and 30.7% (5089/16 595) of all the inpatients the cause of burn was related to Guo-lian-kang (group SF). The patients in group SF admitted to the 322nd Hospital of PLA accounted for 34.2% of all the inpatients admitted to this hospital (1803/5267), more than the other two hospitals in this study. The number of patients in group C was 11 506, accounted for 69.3% of all the inpatients. The age of patients ranged from 8 months to 5 years in group SF and 1 month to 12 years in group C. The age of the majority of patients ranged from 1 to 3 years in both groups. The ratio of male to female was 2.1:1.0 in group SF and 1.4:1.0 in group C. The incidence of scald involving multiple body parts in group SF (3590 cases accounting for 70.5%) was obviously higher than that of group C (6311 cases accounting for 54.8%, χ(2) = 361.138, P < 0.01). In both group SF and group C, the incidence in different sites was ranked from high to low as follows: upper limbs, lower limbs, the head-face-neck region, and the trunk. The degree of injury in group SF was much more severe than that of group C (Z = 27.770, P < 0.01). The rate of patients without pre-hospital treatment was 31.2% (1588/5089) in group SF, which was obviously higher than that of group C (24.8%, 2857/11 506, χ(2) = 73.010, P < 0.01). The rate of patients treated with cryotherapy was obviously lower in group SF (14.7%, 747/5089) than in group C (19.6%, 2255/11 506, χ(2) = 57.636, P < 0.01). The rate of patients treated with delayed resuscitation (6 hours after injury) in group SF (31.5%, 1601/5089) was obviously higher than that of group C (7.8%, 897/11 506, χ(2) = 1545.234, P < 0.01). (2) Family background and occurrence regularity: in group SF, 67.3% (3424/5089) of the patients came from farming area, 22.1% (1123/5089) from villages and towns, and 10.7% (542/5089) from urban areas. In group C, 32.4% (3727/11 506) of the patients came from farming area, 48.4% (5570/11 506) from villages and towns, and 19.2% (2209/11 506) from urban areas. Most of the patients in group SF (77.8%, 3958/5089) were injured between October and March, while most of the patients in group C (58.2%, 6697/11 506) were injured between May and October. (3) Outcome and epidemiological variation: the cure rate of patients in group SF was 32.3% (1645/5089), which was obviously lower than that of group C (44.7%, 5143/11 506, χ(2) = 215.615, P < 0.01). The mortality of patients in group SF was 1.6% (79/5089), and it was obviously higher than that of group C (0.4%, 46/11 506, χ(2) = 62.700, P < 0.01). From 1996 to 2001, patients in group SF accounted for 42.5% (2213/5212), while patients in group C accounted for 57.5% (2999/5212) of the inpatients scalded by hot liquid. After taking preventive measures against injury due to Guo-lian-kang, incidence of scald injury in group SF was lowered to 27.1% (2876/10 604), while the incidence in group C remained at 72.9% (7728/10 604) of the inpatients with hot liquid scald from 2002 to 2010. The difference between the two periods was statistically significant (χ(2) = 376.695,P < 0.01). CONCLUSIONS: The defect of construction of Guo-lian-kang is one of the main factors that lead to a high incidence of pediatric burn in the midwest of Inner Mongolia. Installation of a protective bannister between the cooking pot and the "kang (heatable brick bed)" can obviously reduce the incidence of scald injury. Special injury-causing factors, unprofessional pre-hospital treatment of the wound, delayed resuscitation after shock are the main causes of increasing mortality and disability, and they constitute the key targets of prevention and treatment of such injury in future.