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Objective To investigate the expression of LncRNA DLEU1 in ESCC tissues, and its effect on the proliferation and migration of ESCC cells. Methods We collected 58 cases of ESCC tissues and corresponding para-cancerous tissues. RT-qPCR was used to detect the relative expression levels of DLEU1 in ESCC tissues and cells. Log-rank test was used to analyze the relation between the expression of DLEU1 and clinicopathological features. Kaplan-Meier analysis was used to investigate the correlation between the expression of DLEU1 and the survival of ESCC patients. Multivariate Cox regression model was used to evaluate the effect of DLEU1 on the prognosis of ESCC patients. Effects of DLEU1 on the proliferation and migration of Eca9706 cells were evaluated by CCK-8 and wound healing assays, respectively. Results DLEU1 was highly expressed in ESCC tissues (P < 0.01) and significantly correlated with tumor size, TNM stage and lymph node metastasis (all P < 0.05). High expression of DLEU1 was negatively correlated with poor prognosis of ESCC patients (P < 0.01), and DLEU1 was also an independent prognostic risk factor (P < 0.05). Moreover, knockdown of DLEU1 significantly inhibited the proliferation and migration of Eca9706 cells, compared with the control group (P < 0.01). Conclusion DLEU1 is highly expressed in ESCC tissues. The expression of DLEU1 is an independent risk factor for the prognosis of ESCC patients and promotes ESCC cell proliferation and migration.

We investigated the role of long non-coding RNA DLEU1 (deleted in lymphocytic leukemia 1) in the progression of papillary thyroid carcinoma (PTC). DLEU1 levels were higher in PTC cell lines (BHP5-16, TPC-1,8505C, and SW1736) and patient tissues (n=54) than in a human thyroid follicular epithelial cell line (Nthy-ori3-1) or adjacent normal thyroid tissues. High DLEU1 expression correlated positively with lymph node metastasis and advanced clinical stages in PTC patients. Bioinformatics, dual luciferase reporter, and RNA pulldown assays confirmed that DLEU1 directly binds to miR-421. Moreover, bioinformatics and dual luciferase reporter assays showed that miR-421 directly binds to the 3'untranslated region of the rho-related coiled-coil kinase 1 (ROCK1) in TPC-1 cells. PTC patient tissues and cell lines showed high ROCK1 mRNA and protein levels as well as low miR-421 levels. CCK-8, flow cytometry, wound healing, and Transwell invasion assays demonstrated that DLEU1 silencing decreases TPC-1 cell proliferation, survival and progression, but they can be rescued by miR-421 knockdown or ROCK1 overexpression. DLEU1 knockdown in TPC-1 cells decreased in vivo xenograft tumor size and weight compared to controls in nude mice. These findings demonstrate that DLEU1 promotes PTC progression by sponging miR-421 and increasing ROCK1 expression.

Hangbo Li, Jia Huang, Sa Yu, Zhiping Lou Department of Otolaryngology, Zhuji People’s Hospital, Zhuji 311800, People’s Republic of ChinaCorrespondence: Zhiping LouDepartment of Otolaryngology, Zhuji People’s Hospital, #9 Jianmin Road, Zhuji 311800, People’s Republic of ChinaEmail louzp1970@hotmail.comBackground: Cisplatin (DDP) resistance has become an obstacle to chemotherapy for nasopharyngeal carcinoma (NPC) patients. Recent evidences indicate that long noncoding RNAs (lncRNAs) are involved in tumorigenesis and chemoresistance. However, the potential role of lncRNAs in NPC progression remains largely unknown.Methods: First, lncRNA expression profiling in NPC was performed via microarray analysis. To explore the involvement of DLEU1 in DDP resistance, loss-of-function experiments were employed in vitro and in vivo. Bioinformatics analysis, luciferase reporter assay, qRT-PCR, and Western blot assays were used to investigate the underlying mechanisms.Results: Here, we identified 153 differentially expressed lncRNAs. Among them, DLEU1 was remarkably up-regulated in NPC tissues and associated with worse outcome. Knock-down of DLEU1 could sensitize NPC cells to DDP in vitro and in vivo. Further investigations revealed that DLEU1 positively regulated BIRC6 expression via its competing endogenous RNA (ceRNA) activity on miR-381-3p. We also observed that BIRC6 overexpression or miR-381-3p silence could significantly reverse DLEU1-dependent DDP resistance.Conclusion: Our data suggest that DLEU1 acts as an oncogene to promote DDP resistance and BIRC6 expression in NPC through interacting with miR-381-3p, which may help to develop new strategy against NPC chemoresistance.Keywords: DLEU1, cisplatin resistance, nasopharyngeal carcinoma, BIRC6

Hangbo Li, Jia Huang, Sa Yu, Zhiping Lou Department of Otolaryngology, Zhuji People’s Hospital, Zhuji 311800, People’s Republic of ChinaCorrespondence: Zhiping LouDepartment of Otolaryngology, Zhuji People’s Hospital, #9 Jianmin Road, Zhuji 311800, People’s Republic of ChinaEmail louzp1970@hotmail.comBackground: Cisplatin (DDP) resistance has become an obstacle to chemotherapy for nasopharyngeal carcinoma (NPC) patients. Recent evidences indicate that long noncoding RNAs (lncRNAs) are involved in tumorigenesis and chemoresistance. However, the potential role of lncRNAs in NPC progression remains largely unknown.Methods: First, lncRNA expression profiling in NPC was performed via microarray analysis. To explore the involvement of DLEU1 in DDP resistance, loss-of-function experiments were employed in vitro and in vivo. Bioinformatics analysis, luciferase reporter assay, qRT-PCR, and Western blot assays were used to investigate the underlying mechanisms.Results: Here, we identified 153 differentially expressed lncRNAs. Among them, DLEU1 was remarkably up-regulated in NPC tissues and associated with worse outcome. Knock-down of DLEU1 could sensitize NPC cells to DDP in vitro and in vivo. Further investigations revealed that DLEU1 positively regulated BIRC6 expression via its competing endogenous RNA (ceRNA) activity on miR-381-3p. We also observed that BIRC6 overexpression or miR-381-3p silence could significantly reverse DLEU1-dependent DDP resistance.Conclusion: Our data suggest that DLEU1 acts as an oncogene to promote DDP resistance and BIRC6 expression in NPC through interacting with miR-381-3p, which may help to develop new strategy against NPC chemoresistance.Keywords: DLEU1, cisplatin resistance, nasopharyngeal carcinoma, BIRC6

Background miR-146b-5p has been reported to participate in premature ovarian failure (POF) in mice. However, its role in POF patients is unclear. We predicted that miR-146b-5p might interact with lncRNA DLEU1, a crucial player in ovarian cancer. We then explored the interaction between DLEU1 and miR-146b-5p. Methods Expression of DLEU1 and miR-146b-5p in POF and control ovary tissues was determined by RT-qPCR. The subcellular location of DLEU1 in human KGN cells was analyzed using subcellular fractionation assays. The direct interaction between DLEU1 and miR-146b-5p was analyzed using RNA pull-down assays. The role of DLEU1 in miR-146a expression was analyzed using overexpression assay. Cell proliferation was analyzed using cell apoptosis assay. Results Increased DLEU1 expression and decreased miR-146b-5p expression were observed in POF. DLEU1 directly interacted with MiR-146b-5p and was expressed in both nuclear and cytoplasm samples of KGN cells. In KGN cells, DLEU1 and miR-146b-5p failed to regulate the expression of each other. However, DLEU1 promoted cell apoptosis and reduced the inhibitory effects of miR-146b-5p on cell apoptosis. Conclusions DLEU1 is overexpressed in POF and sponges miR-146b-5p to increase KGN cell apoptosis.

Li Feng,1,*Mingyuan He,1,*Min Rao,2 Jiandong Diao,3 Yonggang Zhu11Department of Radiotherapy, China-Japan Union Hospital of Jilin University, Changchun 130033, People’s Republic of China; 2Department of Gastroenterology, The First Hospital of Jilin University, Changchun 130021, People’s Republic of China; 3Department of Oncology and Hematology, China-Japan Union Hospital of Jilin University, Changchun 130033, People’s Republic of China*These authors contributed equally to this workBackground: Long noncoding RNA (lncRNA) deleted in lymphocytic leukemia 1 (DLEU1) was reported to be involved in the development and progression of multiple cancers. However, the accurate expression pattern, biological function and potential molecular mechanism of DLEU1 in glioma are not yet known. The present study investigated the role of DLEU in the development and progression of glioma, as well as the potential mechanism played by DLEU1 in glioma.Materials and methods: The levels of DLEUI in glioma tissues and cell lines were examined using quantitative real-time PCR. The potential effects of DLEU1 on the proliferation, mobility, invasion and apoptosis of glioma cells were evaluated using corresponding in vitro experiments. The association between DLEU1 and microRNA (miR)-421 was also determined using luciferase reporter activity and RNA immunoprecipitation (RIP) assays.Results: The results revealed that DLEU1 was significantly upregulated in glioma tissues and cell lines. Increased DLEU1 was positively associated with the high-grade carcinoma (III–IV). Functional studies revealed that knockdown of DLEU1 expression by siRNA led to decreased proliferation, migration and invasion and increased apoptosis in human glioma cells. Furthermore, luciferase reporter activity and RIP assays confirmed that DLEUI could act as a competing endogenous RNA (ceRNA) for miR-421 that functioned as a tumor suppressor in glioma. Moreover, inhibition miR-421 partially restored the effect of DLEU1 knockdown on the glioma cells. DLEU1 could regulate myocyte enhancer factor 2D (MEF2D) expression, a known target of miR-421 in glioma cells.Conclusion: Taken together, these findings suggested that DLEU1 regulated MEF2D expression to promote glioma progression by sponging miR-421 and that DLEU1 might be a potential therapeutic target for glioma.Keywords: glioma, LncRNA, DLEU1, miR-421, MEF2D

Long non‐coding RNA (lncRNA) deleted in lymphocytic leukaemia 1 (DLEU1) was reported to be involved in the occurrence and development of multiple cancers. However, the exact expression, biological function and underlying mechanism of DLEU1 in hepatocellular carcinoma (HCC) remain unclear. In this study, real‐time quantitative polymerase chain reaction (qRT‐PCR) in HCC tissues and cell lines revealed that DLEU1 expression was up‐regulated, and the increased DLEU1 was closely associated with advanced tumour‐node‐metastasis stage, vascular metastasis and poor overall survival. Function experiments showed that knockdown of DLEU1 significantly inhibited HCC cell proliferation, colony formation, migration and invasion, and suppressed epithelial to mesenchymal transition (EMT) process via increasing the expression of E‐cadherin and decreasing the expression of N‐cadherin and Vimentin. Luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay demonstrated that DLEU1 could sponge miR‐133a. Moreover, miR‐133a inhibition significantly reversed the suppression effects of DLEU1 knockdown on HCC cells. Besides, we found that silenced DLEU1 significantly decreased insulin‐like growth factor 1 receptor (IGF‐1R) expression (a target of miR‐133a) and its downstream signal PI3K/AKT pathway in HCC cells, while miR‐133a inhibitor partially reversed this trend. Furthermore, DLEU1 knockdown impaired tumour growth in vivo by regulating miR‐133a/IGF‐1R axis. Collectively, these findings indicate that DLEU1 promoted HCC progression by sponging miR‐133a to regulate IGF‐1R expression. Deleted in lymphocytic leukaemia 1/miR‐133a/IGF‐1R axis may be a novel target for treatment of HCC.

Objective To explore the role of long non-coding RNA DLEU1 in the tumorigenesis and progression of non-small cell lung cancer (NSCLC) and the underlying mechanisms. Methods The expression of DLEU1 in NSCLC tumor tissues and adjacent normal tissues was evaluated using bioinformatics analysis and qPCR. The effects of DLEU1 overexpression or deficiency on cell proliferation, apoptosis, migration and invasion were explored experimentally. Additionally, the impact of DLEU1 up-regulation on tumourigenesis was also assessed in vivo. Results The expression of DLEU1 was up-regulated in NSCLC tumor tissues. DLEU1 overexpression promoted the proliferation, migration, and invasion, but inhibited the apoptosis of NSCLC cells by upregulating CDK1 expression, binding with SRC and altering the expression of P70(S6K), MMP2 and E-cadherin. Besides, xenograft tumors in nude mice demonstrated that DLEU1 overexpression accelerated tumor growth. Conclusions DLEU1 promoted tumorigenesis and progression of NSCLC, and might be a promising therapeutic target for NSCLC.

Growing evidences suggest that long non-coding RNAs (lncRNAs) are closely correlated to the development of human cancer, such as colorectal cancer (CRC). A previous report suggested that DLEU1 accelerated CRC development. However, DLEU1’s underlying mechanism in CRC remains unclear. In our study, the level of DLEU1 in CRC tissues is investigated by qRT-PCR. Our data exhibited that DLEU1 level was observably increased in CRC tissues and CRC cell lines and was closely associated with bad prognosis of CRC patients. CRC cell proliferation was repressed by sh-LncRNA DLEU1, whereas cell apoptosis was markedly stimulated. Moreover, knockdown of DLEU1 inhibited cell migration and invasion. Mechanistically, through interacting with miR-320b in CRC, DLEU1 promoted the level of PRPS1 which was a target of miR-320b. The rescue experiment confirmed that knockdown of DLEU1 repressed cell proliferation, migration and invasion while stimulated cell apoptosis via miR-320b/phosphoribosyl pyrophosphate synthetase 1 (PRPS1) axis. Meanwhile, the data of xenograft model exhibited that inhibition of DLEU1 suppressed tumor growth in vivo. In summary, DLEU1 knockdown may repress PRPS1 expression via miR-320b, and then repress cell proliferation, migration and invasion while stimulate cell apoptosis. Our research may provide a novel target for the treatment of CRC.

Feng L, He M, Rao M, Diao J, Zhu Y. Onco Targets Ther. 2019;12:5405–5414. The Editor and Publisher of OncoTargets and Therapy wish to retract the published article. The authors initially raised concerns that two of the glioma cell lines (LN229 and A172) reported in the study had been contaminated with HeLa cells. The authors advised that they were unable to provide the original raw data for their study and thus were unable to verify its findings. The authors also advised the study did not have approval from the China-Japan Union Hospital of Jilin University ethical committee prior to commencement. This is despite a statement within the article stating that approval had been given. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Background Neuropathic pain belongs to chronic pain and is caused by the primary dysfunction of the somatosensory nervous system. Long noncoding RNAs (lncRNAs) have been reported to regulate neuronal functions and play significant roles in neuropathic pain. DLEU1 has been indicated to have close relationship with neuropathic pain. Therefore, our study focused on the significant role of DLEU1 in neuropathic pain rat models. Methods We first constructed a chronic constrictive injury (CCI) rat model. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were employed to evaluate hypersensitivity in neuropathic pain. RT-qPCR was performed to analyze the expression of target genes. Enzyme-linked immunosorbent assay (ELISA) was conducted to detect the concentrations of interleukin‐6 (IL-6), tumor necrosis factor‐α (TNF-α) and IL-1β. The underlying mechanisms of DLEU1 were investigated using western blot and luciferase reporter assays. Results Our findings showed that DLEU1 was upregulated in CCI rats. DLEU1 knockdown reduced the concentrations of IL‐6, IL‐1β and TNF‐α in CCI rats, suggesting that neuroinflammation was inhibited by DLEU1 knockdown. Besides, knockdown of DLEU1 inhibited neuropathic pain behaviors. Moreover, it was confirmed that DLEU1 bound with miR-133a-3p and negatively regulated its expression. SRPK1 was the downstream target of miR-133a-3p. DLEU1 competitively bound with miR-133a-3p to upregulate SRPK1. Finally, rescue assays revealed that SRPK1 overexpression rescued the suppressive effects of silenced DLEU1 on hypersensitivity in neuropathic pain and inflammation of spinal cord in CCI rats. Conclusion DLEU1 regulated inflammation of the spinal cord and mediated hypersensitivity in neuropathic pain in CCI rats by binding with miR-133a-3p to upregulate SRPK1 expression.

Mounting studies have revealed that long non-coding RNA (lncRNA) deleted in lymphocytic leukemia 1 (DLEU1) positively regulated the initiation and development of various human malignant tumors. Nevertheless, the function and mechanism of DLEU1 in human glioblastoma multiforme (GBM) remain elusive and ill-defined. The current study was designed to highlight the functional role and disclose the underlying molecular mechanism by which DLEU1 regulated GBM development. We found that DLEU1 was up-regulated in GBM and DLEU1 knockdown significantly inhibited GBM cell proliferation and induced apoptosis. As predicted by bioinformatics analysis and validated in mechanistic assays, SP1 could bind to the promoter region of DLEU1 to activate DLEU1 transcription. Additionally, miR-4429 was verified as a target gene of DLEU1 and negatively modulated by DLEU1. More importantly, miR-4429 overexpression repressed the mRNA and protein levels of SP1 via binding to the 3′UTR of SP1. Overexpression of SP1 or miR-4429 inhibitor could partly abolish the effect of DLEU1 knockdown on cell viability and apoptosis in GBM. Accordingly, our experimental data revealed that SP1–DLEU1–miR-4429 formed a feedback loop to promote GBM development, providing a new evidence for the role of DLEU1 in GBM.

Recently, a large number of studies have focused on the important role of long non‐coding RNAs (lncRNAs) in metabolism and development and have found that abnormal lncRNA expression is associated with the pathogenesis and development of many diseases. The lncRNA DLEU1 is involved in many solid tumours and haematological malignancies. However, its role in epithelial ovarian carcinoma (EOC) and the associated molecular mechanisms has not been reported. In this study, quantitative reverse transcription–PCR (qRT–PCR) demonstrated higher lncRNA DLEU1 expression in EOC tissues than in normal tissues. Plasmid transfection of DLEU1 to up‐regulate its expression in the ovarian cancer cell lines A2780 and OVCAR3 increased cell proliferation, migration, and invasion, while inhibited apoptosis. Nude mouse xenograft assay demonstrated that DLEU1 overexpression promoted tumour growth in vivo. QRT–PCR showed decreased miR‐490‐3p expression, while Western blotting demonstrated increased its target genes CDK1, cyclinD1 and SMARCD1, as well as matrix metalloproteinase‐2 (MMP2), Bcl‐xL and P70S6K protein expression, respectively. Short interfering RNA silencing of DLEU1 produced opposite results, where qRT–PCR showed increased miR‐490‐3p expression. The dual‐luciferase reporter assay revealed a direct interaction between DLEU1 and miR‐490‐3p. MiR‐490‐3p plays a tumour suppressor role in epithelial ovarian cancer by targeting CDK1 regulation and influencing SMARCD1 and cyclin D1 (CCND1) expressions. Therefore, we suggest that through interaction with miR‐490‐3p, DLEU1 may influence the expression of CDK1, CCND1 and SMARCD1 protein, subsequently promoting the development and progression of EOC.

Li Feng,1,*Mingyuan He,1,*Min Rao,2 Jiandong Diao,3 Yonggang Zhu11Department of Radiotherapy, China-Japan Union Hospital of Jilin University, Changchun 130033, People’s Republic of China; 2Department of Gastroenterology, The First Hospital of Jilin University, Changchun 130021, People’s Republic of China; 3Department of Oncology and Hematology, China-Japan Union Hospital of Jilin University, Changchun 130033, People’s Republic of China*These authors contributed equally to this workBackground: Long noncoding RNA (lncRNA) deleted in lymphocytic leukemia 1 (DLEU1) was reported to be involved in the development and progression of multiple cancers. However, the accurate expression pattern, biological function and potential molecular mechanism of DLEU1 in glioma are not yet known. The present study investigated the role of DLEU in the development and progression of glioma, as well as the potential mechanism played by DLEU1 in glioma.Materials and methods: The levels of DLEUI in glioma tissues and cell lines were examined using quantitative real-time PCR. The potential effects of DLEU1 on the proliferation, mobility, invasion and apoptosis of glioma cells were evaluated using corresponding in vitro experiments. The association between DLEU1 and microRNA (miR)-421 was also determined using luciferase reporter activity and RNA immunoprecipitation (RIP) assays.Results: The results revealed that DLEU1 was significantly upregulated in glioma tissues and cell lines. Increased DLEU1 was positively associated with the high-grade carcinoma (III–IV). Functional studies revealed that knockdown of DLEU1 expression by siRNA led to decreased proliferation, migration and invasion and increased apoptosis in human glioma cells. Furthermore, luciferase reporter activity and RIP assays confirmed that DLEUI could act as a competing endogenous RNA (ceRNA) for miR-421 that functioned as a tumor suppressor in glioma. Moreover, inhibition miR-421 partially restored the effect of DLEU1 knockdown on the glioma cells. DLEU1 could regulate myocyte enhancer factor 2D (MEF2D) expression, a known target of miR-421 in glioma cells.Conclusion: Taken together, these findings suggested that DLEU1 regulated MEF2D expression to promote glioma progression by sponging miR-421 and that DLEU1 might be a potential therapeutic target for glioma.Keywords: glioma, LncRNA, DLEU1, miR-421, MEF2D

Although accumulating evidence has shown the important function of long non-coding RNAs (lncRNAs) in tumor progression and chemotherapy resistance, the role of lncRNA DLEU1 in regulating proliferation, invasion, and chemoresistance of bladder cancer (BCA) cells remains largely unknown. Here, we found that DLEU1 was upregulated in BLCA tissues and BCA patients with high DLEU1 expression exhibited a shorter survival time. Furthermore, mechanistic analysis and functional assays validated that DLEU1 induced cell proliferation, invasion, and cisplatin resistance of BCA cells by de-repressing the expression of HS3ST3B1 through sponging miR-99b. Low miR-99b and high HS3ST3B1 levels were correlated with worse prognosis in patients with BCA. Ectopic expression of HS3ST3B1 or inhibition of miR-99b reversed DLEU1 knockdown-mediated suppression of cell proliferation, invasion, and cisplatin resistance. Thus, our study revealed a novel role for the DLEU1/miR-99b/HS3ST3B1 axis in regulating proliferation, invasion, and cisplatin resistance of BCA cells.

Although growing evidence has demonstrated that the long non-coding RNA DLEU1 is involved in the progression of various cancers, its functional role and underlying mechanisms have not been explored in cervical cancer (CC). In this study, we found that DLEU1 was up-regulated in both CC tissues and CC cell lines, and overexpression of DLEU1 was significantly correlated with shorter patient survival. Knockdown of DLEU1 suppressed CC cell proliferation and invasion, whereas overexpression of DLEU1 promoted the proliferation and invasion of CC cells. Bioinformatics analysis was used to elucidate the potential correlation between DLEU1 and miR-381. Moreover, qRT-PCR analysis, luciferase reporter assay and RNA immunoprecipitation assay confirmed that DLEU1 inhibited the expression of miR-381, and revealed a direct interaction between DLEU1 and miR-381. In addition, we demonstrated that miR-381 directly targeted HOXA13 in CC cells. The restoration of HOXA13 expression reversed DLEU1 knockdown or miR-381 overexpression-mediated suppression of cell proliferation and invasion. These results suggested that DLEU1 can promote CC cell proliferation and invasion via the miR-381/HOXA13 axis.

Background Accumulating evidences show that long noncoding RNAs (lncRNA) play essential roles in the development and progression of various malignancies. However, their functions remains poorly understood and many lncRNAs have not been defined in colorectal cancer (CRC). In this study, we investigated the role of DLEU1 in CRC. Methods Quantitative real-time PCR was used to detect the expression of DLEU1 and survival analysis was adopted to explore the association between DLEU1 expression and the prognosis of CRC patients. CRC cells were stably transfected with lentivirus approach and cell proliferation, migration, invasion and cell apoptosis, as well as tumorigenesis in nude mice were performed to assess the effects of DLEU1 in BCa. Biotin-coupled probe pull down assay, RNA immunoprecipitation and Fluorescence in situ hybridization assays were conducted to confirm the relationship between DLEU1 and SMARCA1. Results Here we revealed that DLEU1 was crucial for activation of KPNA3 by recruiting SMARCA1, an essential subunit of the NURF chromatin remodeling complex, in CRC. DLEU1 was indispensible for the deposition of SMARCA1 at the promoter of KPNA3 gene. Increased expression of DLEU1 and KPNA3 was observed in human CRC tissues. And higher expression of DLEU1 or KPNA3 in patients indicates lower survival rate and poorer prognosis. DLEU1 knockdown remarkably inhibited CRC cell proliferation, migration and invasion in vitro and in vivo while overexpressing KPNA3 in the meantime reversed it. Conclusions Our results identify DLEU1 as a key regulator by a novel DLEU1/SMARCA1/KPNA3 axis in CRC development and progression, which may provide a potential biomarker and therapeutic target for the management of CRC. Electronic supplementary material The online version of this article (10.1186/s12943-018-0873-2) contains supplementary material, which is available to authorized users.

Genome-wide study in Germans identifies four novel multiple sclerosis risk genes and confirms already known gene loci., We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis.