A novel long non-coding RNA SLNCR1 promotes proliferation, migration, and invasion of melanoma via transcriptionally regulating SOX5.

Steroid receptor RNA activator (SRA)-like non-coding RNA (SLNCR1) has been implicated in various tumorigenic processes, but the precise regulatory role in melanoma progression remains uncertain. We performed a comprehensive analysis to investigate the prognostic value of SLNCR1 expression in patients with melanoma by TCGA database and melanoma tissue samples via the Kaplan-Meier method. Subsequently, we conducted qRT-PCR and Fluorescence in Situ Hybridization (FISH) assays to identify SLNCR1 expression levels and localization in tissues and cells, respectively. Loss-of-function assays utilizing shRNAs vectors were used to investigate the potential impact of SLNCR1. Our data showed that SLNCR1 is significantly up-regulated in human malignant melanoma tissues and cell lines and functions as an oncogene. Silencing of SLNCR1 suppressed melanoma cell proliferation, migration, invasion, and inhibited tumorigenesis in a mouse xenograft model. Additionally, we employed bioinformatic predictive analysis, combined with dual-luciferase reporter analysis and functional rescue assays, to elucidate the mechanistic target of the SLNCR1/SOX5 axis in melanoma. Mechanistically, we discovered that SLNCR1 promotes EMT of human melanoma by targeting SOX5, as downregulation of SLNCR1 expression leads to a decrease in SOX5 protein levels and inhibits melanoma tumorigenesis. Our research offers promising insights for more precise diagnosis and treatment of human melanoma.

Effect of anti-skin disorders of ginsenosides- A Systematic Review.

Ginsenosides are bioactive components of Panax ginseng with many functions such as anti-aging, anti-oxidation, anti-inflammatory, anti-fatigue, and anti-tumor. Ginsenosides are categorized into dammarane, oleanene, and ocotillol type tricyclic triterpenoids based on the aglycon structure. Based on the sugar moiety linked to C-3, C-20, and C-6, C-20, dammarane type was divided into protopanaxadiol (PPD) and protopanaxatriol (PPT). The effects of ginsenosides on skin disorders are noteworthy. They play anti-aging roles by enhancing immune function, resisting melanin formation, inhibiting oxidation, and elevating the concentration of collagen and hyaluronic acid. Thus, ginsenosides have previously been widely used to resist skin diseases and aging. This review details the role of ginsenosides in the anti-skin aging process from mechanisms and experimental research.

Multi-scale sequential feature selection for disease classification using Raman spectroscopy data.

Raman spectroscopy (RS) optical technology promises non-destructive and fast application in medical disease diagnosis in a single step. However, achieving clinically relevant performance levels remains challenging due to the inability to search for significant Raman signals at different scales. Here we propose a multi-scale sequential feature selection method that can capture global sequential features and local peak features for disease classification using RS data. Specifically, we utilize the Long short-term memory network (LSTM) module to extract global sequential features in the Raman spectra, as it can capture long-term dependencies present in the Raman spectral sequences. Meanwhile, the attention mechanism is employed to select local peak features that were ignored before and are the key to distinguishing different diseases. Experimental results on three public and in-house datasets demonstrate the superiority of our model compared with state-of-the-art methods for RS classification. In particular, our model achieves an accuracy of 97.9 ± 0.2% on the COVID-19 dataset, 76.3 ± 0.4% on the H-IV dataset, and 96.8 ± 1.9% on the H-V dataset.

Role of Circular RNAs in the Pathogenesis of Malignant Melanoma.

Malignant melanoma is one of the most aggressive types of skin cancer. Thus, efficient diagnosis and treatment methods are crucial for advanced melanoma. Circular RNAs (circRNAs) have been regarded as a 'splicing noise' in the past decades. However, several circRNAs have been recently reported to be differentially expressed in melanoma, and the cell or tissue-specific expression makes these suitable candidate diagnostic or therapeutic biomarkers. In addition, emerging studies have confirmed that circular RNAs play pivotal roles in the proliferation, invasion, metastasis, and migration of malignant melanoma. However, specific pathogenic mechanisms between melanoma and circRNAs remain unclear. In the present study, it was summarized that circRNAs are associated with the pathogenesis of melanoma, including hsa_circ_0083444, hsa_circ_0005320, hsa_circ_0067531, hsa_circ_0084043, hsa_circ_0000082, hsa_circ_0016418, hsa_circ_0085533 and hsa_circ_0025039, hsa_circ_0001946, hsa_circ_0002770, hsa_circ_0079593, hsa_circ_0027247, hsa_circ_0017247, hsa_circ_0020710. These can provide potential diagnosis, treatment, and prognostication biomarkers for advanced melanoma in clinical applications.

The Prognostic Value of LncRNA SLNCR1 in Cancers: A Meta-Analysis.

OBJECTIVE: This meta-analysis was performed to identify the prognostic value of SLNCR1 in multiple cancer types. METHODS: Electronic databases, including PubMed, EMBASE, and Web of Science, Cochrane Library, Medline, BioMed Central, Springer, Science Direct, and China National Knowledge Internet (CNKI), were searched for relevant studies up to August 2021, and the hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated to assess the relationship between SLNCR1 expression and overall survival (OS). RESULTS: 12 studies with a total of 1155 patients with 9 different types of cancers were included in this meta-analysis. The pooled HR indicates that high SLNCR1 expression represented poorer prognosis of cancer (HR = 2.11, 95% CI: 1.59-2.80, I 2 = 0%, P < 0.00001). Additionally, high SLNCR1 expression was correlated with TNM stage (odds ratio (OR): 1.72, 95% CI: 1.08-2.74, I 2 = 62%, P=0.02), lymph node metastasis (LNM) (OR:2.42, 95% CI: 1.61-3.64, I 2 = 55%, P < 0.0001), and distant metastases (DM) (OR: 2.30, 95% CI: 1.50-3.55, I 2 = 27%, P=0.0002). However, no evidence was found for a relationship between SLNCR1 expression and clinical features such as tumor size (OR: 1.71, 95% CI: 0.93-3.14, I 2 = 71%, P=0.09), age (OR: 0.86, 95% CI: 0.68-1.08, I 2 = 0%, P=0.19), or gender (OR: 1.07, 95% CI: 0.64-1.81, I 2 = 55%, P=0.79). CONCLUSION: Our findings found that high SLNCR1 expression was associated with poor OS, advanced tumor stage, tumor size, LNM, and DM in multiple cancers, indicating that SLNCR1 may serve as a potential prognostic biomarker for cancer patients in China.

Effect of EG00229 on Radiation Resistance of Lung Adenocarcinoma Cells.

Background: Neuropilin 1 (NRP1) is a pleiotropic receptor that interacts with multiple ligands and their receptors and plays a critical role in the process of tumor metastasis and radiation resistance in endothelial cells and tumor cells. In this study, we sought to investigate the mechanistic role of NRP1 in the radiation resistance of non-small cell lung cancer (NSCLC) cells and the role of EG00229 (an inhibitor of NRP1) on reversing radiation resistance. Materials and Methods: A549 and H1299 NSCLC cells were used to construct radiation resistance models. Western blot, ELISA, and qRT-PCR were used to detect protein and mRNA levels of NRP1, epithelial-mesenchymal transition (EMT) markers, and molecules in signaling pathways. Immunofluorescence was used to measure changes in co-expression of NRP1 and VEGF-165 in radiation-resistant model cells. An immunoprecipitation assay was used to detect the binding capacity of NRP1 and VEGF-165. Results: We successfully created two radiation resistant models (A549RR and H1299-RR). The expression levels of NRP1, EMT-related proteins, and proteins in metastasis-related pathways were increased in NSCLC cells with radiation resistance. After adding EG00229, the expression levels and binding capacity of NRP1 and VEGF-165 proteins were significantly reduced. The expression of EMT-related proteins and proteins in metastasis-related pathways were reduced in NSCLC cells with radiation resistance. Conclusion: Our data provide an insight into the molecular mechanisms of radiation resistance and suggest that EG00229 may contribute to reversing the radiation resistance of NSCLC cells by inhibiting the binding of NRP1 and VEGF-165. Our findings could provide a novel theoretical and experimental foundation for improving the efficacy of lung cancer radiotherapy.

Pivotal factors associated with the immunosuppressive tumor microenvironment and melanoma metastasis.

BACKGROUND: Considering melanoma is the deadliest malignancy among dermatoma and presently lacks effective therapies, there is an urgent need to investigate the potential mechanisms underlying melanoma metastasis and determine prospective therapeutic targets for precise treatment of melanoma. METHOD: Hub genes in melanoma metastasis were identified by analyzing RNA-seq data (mRNA, miRNA, and lncRNA) obtained from TCGA database. Then the identified hub genes were validated in human tissues with qRT-PCR, followed by survival analysis. Competing endogenous RNAs of the hub genes were defined to clarify potential molecular mechanism of melanoma progression. Then central gene-related signaling pathways were analyzed, followed by immune cell abundance analysis in tumor microenvironment with CYTERSORTx. RESULT: A tetrad of IL2RA, IL2RG, IFNG, and IL7R genes were determined as hub genes and verified by qRT-PCR, which were significantly associated with unfavorable prognosis in melanoma. LINC02446, LINC01857, and LINC02384 may act as competing endogenous lncRNAs of IL2RA and IL7R through absorbing their shared miR.891a.5p and miR.203b.3p. JAK-STAT signaling pathway identified as the most relevant pathway in melanoma metastasis, as well as a wealthy of genes including TNFRSF 13B, TNFRSF17, TNFRSF9, TNFRSF8, TNFRSF13C, TNFRSF11B, LAG3, NRP1, ENTPD1, NT5E, CCL21, and CCR7, may induce tumor autoimmune suppression through enhancing regulatory T-cell abundance and performance in the tumor microenvironment. And regulatory T-cell proportion was indeed critically elevated in metastatic melanoma relative to primary melanoma, as well as in highly expressed IL2RA, IL2RG, IL7R, and IFNG group than their respective counterparts. CONCLUSION: Elevated IL2RA, IL2RG, IL7R, and IFNG expression may play a central role in promoting melanoma metastasis through up regulation of intratumoral regulatory T-cell proportion mainly by activation of JAK-STAT signaling pathway. LINC02446, LINC01857, and LINC02384 may stimulate melanoma progression by reducing tumor-protecting miR.891a.5p and miR.203b.3p. A number of identified molecules including TNFRSF13B, LAG3, NRP1, ENTPD1, NT5E, CCL21, and CCR7 can serve as future therapeutic targets in melanoma treatment.

Prognostic Value of ctDNA Mutation in Melanoma: A Meta-Analysis.

PURPOSE: Melanoma is the most aggressive form of skin cancer. Circulating tumor DNA (ctDNA) is a diagnostic and prognostic marker of melanoma. However, whether ctDNA mutations can independently predict survival remains controversial. This meta-analysis assessed the prognostic value of the presence or change in ctDNA mutations in melanoma patients. METHODS: We identified studies from the PubMed, EMBASE, Web of Science, and Cochrane databases. We estimated the combined hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) using either fixed-effect or random-effect models based on heterogeneity. RESULTS: Sixteen studies including 1,781 patients were included. Both baseline and posttreatment detectable ctDNA were associated with poor OS (baseline detectable vs. undetectable, pooled HR = 1.97, 95% CI = 1.64-2.36, P < 0.00001; baseline undetectable vs. detectable, pooled HR = 0.19, 95% CI = 0.11-0.36, P < 0.00001; posttreatment detectable vs. undetectable, pooled HR = 2.36, 95% CI = 1.30-4.28, P=0.005). For PFS, baseline detectable ctDNA may be associated with adverse PFS (baseline detectable vs. undetectable, pooled HR = 1.41, 95% CI = 0.84-2.37, P=0.19; baseline undetectable vs. detectable, pooled HR = 0.43, 95% CI = 0.19-0.95, P=0.04) and baseline high ctDNA and increased ctDNA were significantly associated with adverse PFS (baseline high vs. low/undetectable, pooled HR = 3.29, 95% CI = 1.73-6.25, P=0.0003; increase vs. decrease, pooled HR = 4.48, 95% CI = 2.45-8.17, P < 0.00001). The baseline BRAFV600 ctDNA mutation-positive group was significantly associated with adverse OS compared with the baseline ctDNA-negative group (pooled HR = 1.90, 95% CI = 1.58-2.29, P < 0.00001). There were no significant differences in PFS between the baseline BRAFV600 ctDNA mutation-detectable group and the undetectable group (pooled HR = 1.02, 95% CI = 0.72-1.44, P=0.92). CONCLUSION: The presence or elevation of ctDNA mutation or BRAFV600 ctDNA mutation was significantly associated with worse prognosis in melanoma patients.

Effects of MLL5 and HOXA regulated by NRP1 on radioresistance in A549.

Radiotherapy is widely used in the management of lung cancer, and physicians are aware that the effect of radiotherapy is dependent on radiosensitivity. Although a series of blockers and activators targeting molecules related to radioresistance have been developed as radiation sensitizers, compensatory mechanisms or drug resistance limits their clinical efficacy. The identification of a key molecule related to lung cancer cell radioresistance or an effective molecular target is a challenging but important problem in radiation oncology. A previous study found that neuropilin 1 (NRP1) is related to radioresistance in A549 cells and is associated with VEGF, PI3K-Akt, MAPK-ERK, P38, NF-κß and TGF-ß. Inhibition of NRP1 can increase the radiosensitivity of A549 cells. Therefore, NRP1 may be a molecular target for radiotherapy-sensitizing drugs in lung cancer. The present study investigated the key downstream genes of NRP1, verified their regulation and clarified their roles in regulating lung cancer radioresistance. NRP1 positively regulated the downstream homeobox genes (HOXs) HOXA6, HOXA9 and mixed lineage leukaemia 5 (MLL5) in addition to MLL5-regulated HOXA6 and HOXA9, but these genes did not regulate NRP1. MLL5, HOXA6 and HOXA9 levels were decreased in tumour tissues and positively correlated with NRP1. All of these genes were induced by ionizing radiation in vivo and in vitro. NRP1 expression was significantly lower in squamous cell carcinoma compared with that in adenocarcinoma, and lymph node metastasis occurred more often in patients with lung cancer with high MLL5 and NRP1 expression compared with patients with low MLL5 and NRP1 expression. Collectively, these data confirmed that NRP1 is associated with MLL5 and regulates radioresistance through HOXA6 and HOXA9.

Identification of Potential BRAF Inhibitor Joint Therapy Targets in PTC based on WGCAN and DCGA.

As the most common mutation in papillary thyroid cancer (PTC), B-type Raf kinase V600E mutation (BRAFV600E ) has become an important target for the clinical treatment of PTC. However, the clinical application still faces the problem of resistance to BRAF inhibitors (BRAFi). Therefore, exploring BRAFV600E-associated prognostic factors to providing potential joint targets is important for combined targeted therapy with BRAFi. In this study, we combined transcript data and clinical information from 199 BRAF wild-type (BRAFWT ) patients and 283 BRAFV600E mutant patients collected from The Cancer Genome Atlas (TCGA), and screened 455 BRAFV600E- associated genes through differential analysis and weighted gene co-expression network analysis. Based on these BRAFV600E -associated genes, we performed functional enrichment analysis and co-expression differential analysis and constructed a core co-expression network. Next, genes in the differential co-expression network were used to predict drugs for therapy in the crowd extracted expression of differential signatures (CREEDS) database, and the key genes were selected based on the hub co-expression network through survival analyses and receiver operating characteristic (ROC) curve analyses. Finally, we obtained eight BRAFV600E -associated biomarkers with both prognostic and diagnostic values as potential BRAFi joint targets, including FN1, MET, SLC34A2, NGEF, TBC1D2, PLCD3, PROS1, and NECTIN4. Among these genes, FN1, MET, PROS1, and TBC1D2 were validated through GEO database. Two novel biomarkers, PROS1 and TBC1D2, were further validated by qRT-PCR experiment. Besides, we obtained four potential targeted drugs that could be used in combination with BRAFi to treat PTC, including MET inhibitor, ERBB3 inhibitor, anti-NaPi2b antibody-drug conjugate, and carboplatin through literature review. The study provided potential drug targets for combination therapy with BRAFi for PTC to overcome the drug resistance for BRAFi.

Patient-Derived Organoids in Precision Medicine: Drug Screening, Organoid-on-a-Chip and Living Organoid Biobank.

Organoids are in vitro self-assembling, organ-like, three-dimensional cellular structures that stably retain key characteristics of the respective organs. Organoids can be generated from healthy or pathological tissues derived from patients. Cancer organoid culture platforms have several advantages, including conservation of the cellular composition that captures the heterogeneity and pharmacotypic signatures of the parental tumor. This platform has provided new opportunities to fill the gap between cancer research and clinical outcomes. Clinical trials have been performed using patient-derived organoids (PDO) as a tool for personalized medical decisions to predict patients' responses to therapeutic regimens and potentially improve treatment outcomes. Living organoid biobanks encompassing several cancer types have been established, providing a representative collection of well-characterized models that will facilitate drug development. In this review, we highlight recent developments in the generation of organoid cultures and PDO biobanks, in preclinical drug discovery, and methods to design a functional organoid-on-a-chip combined with microfluidic. In addition, we discuss the advantages as well as limitations of human organoids in patient-specific therapy and highlight possible future directions.

A meta-analysis of fractional CO2 laser combined with PRP in the treatment of acne scar.

This study aimed to analyze the effectiveness and safety of ablative fractional carbon dioxide laser systems (CO2 AFL) combined with autologous platelet-rich plasma (PRP) in the treatment of acne scars through the retrieval and collection of related literature to further guide the treatment of acne scars. We searched Web of Science, PubMed, Embase, Wanfang Data, Chinese National Knowledge Infrastructure, and VIP Database. All randomized and nonrandomized controlled trials on CO2 AFL combined with PRP in the treatment of acne scars were included, and Revman5.3 systematic review software was used in the meta-analysis. Nine studies were included in this meta-analysis. The data analysis results showed that the CO2 AFL combined with PRP treatment group showed significantly better results than the pure CO2 AFL control group in terms of clinical improvement score, clinical improvement rate, patient satisfaction, and crusting period. The results of this meta-analysis showed that CO2 AFL combined with PRP in the treatment of acne scars is more effective and safer than CO2 AFL alone.

α-MSH-PE38KDEL Kills Melanoma Cells via Modulating Erk1/2/MITF/TYR Signaling in an MC1R-Dependent Manner.

BACKGROUND/OBJECTIVE: The immunotoxin α-MSH-PE38KDEL consisting of α-MSH and PE38KDEL showed high cytotoxicity on MSH receptor-positive melanoma cells, suggesting that α-MSH-PE38KDEL might be a potent drug for the treatment of melanoma. Herein, we explored whether the Erk1/2/MITF/TYR signaling, a verified target of α-MSH/MC1R, was involved in α-MSH-PE38KDEL-mediated cytotoxicity. METHODS: Human melanoma cell line A375, mouse melanoma cell line B16-F10, human breast cancer cell line MDA-MB-231 and human primary epidermal melanocytes (HEMa) with different expression levels of MC1R were used in this study. Cell apoptosis and viability were determined by using flow cytometry and MTT assays. Protein expressions were tested by Western blotting. RESULTS: The expression levels of MC1R in A375 and B16-F10 cells were significantly higher than that of MDA-MB-231 and HEMa. α-MSH-PE38KDEL treatment induced a significant inhibition in cell viability in A375 and B16-F10 cells, while showed no obvious influence in the viability of MDA-MB-231 and HEMa cells. However, knockdown of MC1R abolished α-MSH-PE38KDEL role in promoting cell apoptosis in A375 and B16-F10 cells, and upregulation of MC1R endowed α-MSH-PE38KDEL function to promote cell apoptosis in MDA-MB-231 and HEMa cells. Additionally, α-MSH-PE38KDEL treatment increased the phosphorylation levels of Erk1/2 and MITF (S73), and decreased MITF and TYR expressions in an MC1R-dependent manner. All of the treatments, including inhibition of Erk1/2 with PD98059, MC1R downregulation and MITF overexpression weakened the anti-tumor role of α-MSH-PE38KDEL in melanoma. CONCLUSION: Collectively, this study indicates that α-MSH-PE38KDEL promotes melanoma cell apoptosis via modulating Erk1/2/MITF/TYR signaling in an MC1R-dependent manner.

Effects of Exogenous Hormones and Reproductive Factors on Female Melanoma: A Meta-Analysis.

Epidemiological findings on the effects of hormones on melanoma risk have been inconsistent. We therefore conducted a meta-analysis to examine the relationship between exogenous hormonal and reproductive factors and the risk of melanoma in women. We performed a search of PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI) database through April 2020 for relevant studies. Based on heterogeneity, we performed the meta-analysis of the risk estimates using either fixed effect or random effect models. We identified 38 studies that met the analytical criteria, involving 3,571,910 participants. The results showed that long-term use of oral contraceptives (OC) may increase the risk of melanoma in women (≥5 years [pooled RR=1.18; 95% CI: 1.07-1.31; I2=0%] and ≥10 years [pooled RR=1.25; 95% CI: 1.06-1.48; I2=0%]). Women who first used OC 15-19 years previously were more likely to develop melanoma (pooled RR=1.52; 95% CI: 1.03-2.24; I2=0%), while the years since the last use and the age at first use were not associated with the development of melanoma in women. Hormone replacement therapy (HRT) increased the incidence of melanoma in women (pooled RR=1.12, 95% CI: 1.02-1.24; I2=50%) and was especially associated with an increased risk of superficial spreading melanoma (SSM) (pooled RR=1.26; 95% CI: 1.17-1.37; I2=0%), and estrogen and estradiol may be the main active agents that contribute to the increased risk of melanoma, but these results may be due to a combination of sun exposure factors. With regard to reproductive factors, decreased parity and being aged ≥20 years at first birth may be associated with an increased risk of melanoma in females, while menopausal status and age at menarche are not associated with the incidence of melanoma in females. Further large-scale prospective studies are necessary to reveal new pathophysiological mechanisms and new therapeutic targets for cutaneous melanoma.

Prognostic Significance of Tumor-Infiltrating Lymphocyte Grade in Melanoma: A Meta-Analysis.

PURPOSE: Tumor-infiltrating lymphocytes (TILs) in primary melanoma are considered to represent the host's antitumor immune response; however, whether TILs can independently predict survival remains controversial. This meta-analysis evaluated the prognostic value of TIL grade for survival in patients with melanoma. METHODS: We identified studies from the PubMed, Web of Science, and China National Knowledge Infrastructure databases to assess the prognostic impact of TIL grade in patients with melanoma. We estimated the combined hazard ratios (HRs) for overall survival (OS), disease-free survival, and disease-specific survival (DSS) at 5 years and end point using either fixed-effect or random-effect models depending on heterogeneity. RESULTS: A total of 13 observational studies including 7,633 patients were enrolled. In the univariate analysis, brisk TIL grade was significantly more strongly correlated with better 5-year OS, 5-year DSS, and end point DSS compared with those of nonbrisk or absent TILs (HR 0.62, 95% CI 0.44-0.88, I2 = 0; HR 0.53, 95% CI 0.30-0.96, I2 = 11%; and HR 0.51, 95% CI 0.30-0.87, I2 = 0, respectively). Compared with absent TIL grade, brisk TIL grade was associated with better 5-year OS and end point OS (HR 0.68, 95% CI 0.50-0.93, I2 = 40% and HR 0.65, 95% CI 0.52-0.83, I2 = 0, respectively). Nonbrisk TIL grade was associated with better end point DSS (HR 0.60, 95% CI 0.44-0.83, I2 = 7%). The multifactor analysis showed that brisk TIL grade was related to better DSS (HR 0.50, 95% CI 0.30-0.90), and nonbrisk or absent TIL grade was correlated with poor DSS (HR 8.7, 95% CI 2.7-40.3). CONCLUSION: Patients with brisk TIL grade had a better prognosis. TIL level deserves further investigation to support the conclusion that it should be routinely included in the pathological report of primary melanoma and in future American Joint Committee on Cancer staging revisions.

miR-30 Family Reduction Maintains Self-Renewal and Promotes Tumorigenesis in NSCLC-Initiating Cells by Targeting Oncogene TM4SF1.

Increasing evidence indicates that tumor-initiating cells (TICs) are responsible for the occurrence, development, recurrence, and development of the drug resistance of cancer. MicroRNA (miRNA) plays a significant functional role by directly regulating targets of TIC-triggered non-small-cell lung cancer (NSCLC), but little is known about the function of the miR-30 family in TICs. In this study, we found the miR-30 family to be downregulated during the spheroid formation of NSCLC cells, and patients with lower miR-30a/c expression had shorter overall survival (OS) and progression-free survival (PFS). Moreover, transmembrane 4 super family member 1 (TM4SF1) was confirmed to be a direct target of miR-30a/c. Concomitant low expression of miR-30a/c and high expression of TM4SF1 correlated with a shorter median OS and PFS in NSCLC patients. miR-30a/c significantly inhibited stem-like characteristics in vitro and in vivo via suppression of its target gene TM4SF1, and then it inhibited the activity of the mTOR/AKT-signaling pathway. Thus, our data provide the first evidence that TM4SF1 is a direct target of miR-30a/c and miR-30a/c inhibits the stemness and proliferation of NSCLC cells by targeting TM4SF1, suggesting that miR-30a/c and TM4SF1 may be useful as tumor biomarkers for the diagnosis and treatment of NSCLC patients.

CYP24A1 Inhibition Facilitates the Antiproliferative Effect of 1,25(OH)2D3 Through Downregulation of the WNT/ß-Catenin Pathway and Methylation-Mediated Regulation of CYP24A1 in Colorectal Cancer Cells.

CYP24A1 is overexpressed in colorectal cancer, and the reason for the dysregulation of CYP24A1 in colorectal cancer is still unknown. In the present study, experiments were designed to test whether CYP24A1 inhibition facilitated the antiproliferative effect of 1,25(OH)2D3. In addition, the role of methylation in the regulation of CYP24A1 expression in human colorectal cancer was investigated. The expression of CYP24A1 in SW480 and Caco2 colorectal cancer cells was inhibited by RNAi. CYP24A1 inhibition significantly increased the antiproliferative effects of 1,25(OH)2D3 in SW480 cells compared with 1,25(OH)2D3 treatment alone (16.78% ± 2.08% vs. 33.53% ± 2.47%, p < 0.05). In addition, CYP24A1 inhibition sensitized Caco2 cells to 1,25(OH)2D3. We also found that CYP24A1 inhibition induced ß-catenin to translocate from the nucleus to the plasma membrane in SW480 cells and enhanced the inhibitory effect of 1,25(OH)2D3 on C-myc. Furthermore, CYP24A1 mRNA expression in Caco2 cells was increased after demethylation treatment, and the expression of CYP24A1 induced by 1,25(OH)2D3 was significantly higher in cells treated with 5-aza-2'-deoxycytidine (DAC) than in an untreated group. In conclusion, inhibition of CYP24A1 expression enhances the antitumor effect of 1,25(OH)2D3 in colorectal cancer, and DNA methylation is involved in the regulation of CYP24A1 expression in a cell-dependent manner.

Association between SORL1 polymorphisms and the risk of Alzheimer's disease.

A meta-analysis was performed to identify empirical data assessing the effects of a single nucleotide polymorphisms of sortilin related receptor on Alzheimer's disease based on 14 studies involving 37941 cases and 49727 control studies. Analysis showed, (i) Increased risk between the single nucleotidepolymorphisms (rs641120, rs1010159) and Alzheimer's disease susceptibility inAsian populations, (ii) Single nucleotide polymorphism rs689021 was associatedwith decreased risk in Caucasians, and (iii) Single nucleotide polymorphismrs641120 was detected as a decreased risk in both populations. Given thesedata, crucial evidence is provided to demonstrate that a significantrelationship exists between SORL1 polymorphisms and susceptibility to Alzheimer's disease.

Identification of miR­124a as a novel diagnostic and prognostic biomarker in non­small cell lung cancer for chemotherapy.

Previous studies have suggested that dysregulation of microRNA (miR) -124a is associated with various types of human cancer. However, there are few studies reporting the level of miR­124a expression in non­small cell lung cancer (NSCLC). The present study investigated the association between miR­124a and NSCLC by analyzing the differential expression of miR­124a in NSCLC using the GEO database, as well as subsequently performing reverse transcription­quantitative polymerase chain reaction analysis on 160 NSCLC biopsies, 32 of which were paired with adjacent normal tissues. The results indicated that mir­124a expression levels were decreased in NSCLC tumor biopsies compared with adjacent normal tissues. The overall survival (OS) in patients with a high expression of miR­124a was prolonged relative to patients with low expression of miR­124a. The expression levels of miR­124a were associated with clinical characteristics, including lymph­node metastasis, tumor differentiation, tumor node metastasis (TNM) stage and diameter. Frequently, lymph­node metastasis, TNM stage, diameter and lack of chemotherapy have been associated with a worse prognosis in patients. In addition, the present study identified that high expression of miR­124awith chemotherapy may increase OS. In conclusion, the current study demonstrated that miR­124a was downregulated in NSCLC, and miR­124a was a potential prognostic tumor biomarker response to chemotherapy.