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Background. Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus (DM). A recent in vitro study found that the suppressor of cytokine signaling 6 (SOCS6) plays a protective role in DR and DM. However, to date, no clinical studies have focused on the role of SOSC6 in DR development. Objectives. The present study aimed to investigate the expression and clinical significance of serum SOCS6 in DR. Materials and methods. A total of 159 DR patients were enrolled in the study. Additionally, 156 type 2 DM (T2DM) patients without DR were recruited as controls. Serum levels of SOCS6, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), vascular endothelial growth factor (VEGF), and angiopoietin-2 (ANG-2) were measured using enzyme-linked immunosorbent assay (ELISA). Demographic and clinical data were collected. Results. Age, the course of DM, systolic blood pressure (SBP), diastolic blood pressure (DBP), and the levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were significantly higher in proliferative DR (PDR) patients. Serum SOCS6 levels in PDR patients were remarkably lower than in non-PDR patients or non-DR T2DM patients. The Pearson's analysis showed that SOCS6 was negatively correlated with CRP, IL-6, TNF-α, IL-1β, VEGF, and ANG-2. The serum levels of CRP, IL-6, TNF-α, IL-1β, VEGF, and ANG-2 in the SOCS6 low expression group were significantly increased compared to patients with high SOCS6 levels. Receiver operating characteristic (ROC) curves showed that SOCS6 could be a potential diagnostic biomarker for DR. For logistic regression, 3 models were used. It was found that SOCS6, the course of DM, SBP and DBP in model 1, IL-1β and TNF-α in model 2, and VEGF and ANG-2 in model 3 were risk factors for DR. Conclusions. The SOCS6 is decreased in DR patients and is related to severity and clinical outcomes, including inflammatory and angiogenic factors. [ABSTRACT FROM AUTHOR]

Background/aim: Exosomes derived from oral squamous cell carcinoma (OSCC) could modulate OSCC development. This study aimed to explore effects of exosome-mediated lncRNA PART1 on OSCC cells. Materials and methods: This study was performed in Tianjin Medical University Cancer Institute from February 2021 to March 2022. Bioinformatic analysis was performed on the public database GEPIA (http://gepia.cancer-pku.cn/). Exosomes isolated from cell lines squamous cell carcinoma 9 (SCC9) and Centre Antoine Lacassagne-27 (CAL27) were identified by transmission electron microscope and western blot. Exosome-mediated lncRNA PART1, microRNA-17-5p(miR-17-5p) and suppressor of cytokine signaling 6(SOCS6) RNA expressions were assessed by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Cell counting kit-8(CCK-8), caspase-3 activity, and flow cytometry were applied to evaluate OSCC cell viabilities and apoptosis. Meanwhile, OSCC cell migratory ability and invasiveness were evaluated using transwell assay. Bindings between miR-17-5p and lncRNA PART1 or SOCS6 were validated using the luciferase reporter test. Western blot was used for detecting the protein levels of SOCS6, phosphorylated signal transducer and activator of transcription 3 (STAT3) and STAT3. Results: According to GEPIA, lncRNA PART1 was downregulated in OSCC tissue samples and cells, and it had a positive correlation with the good prognosis of Head and neck squamous cell cancer (HNSCC) patients. After the exosomes from OSCC cells were isolated and verified, PART1 was then confirmed to be secreted by exosomes. Further, overexpression of exosome-mediated lncRNA PART1 inhibited OSCC cell viabilities, migration, and invasiveness but facilitated OSCC cell apoptosis. PART1 upregulated SOCS6 through sponging miR-17-5p. Moreover, exosome-mediated lncRNA PART1 suppressed the phosphorylation of STAT3. Conclusion: Exosome-mediated lncRNA PART1 could mediate the OSCC progression via miR-17-5p/SOCS6 axis in vitro, suggesting that lncRNA PART1 might be a target for treating OSCC. [ABSTRACT FROM AUTHOR]

This study investigated the role of N6-methyladenosine RNA methylation in liver regeneration following partial hepatectomy in mice. We created a liver-specific knockout mouse model by the deletion of Mettl3, a key component of the N6-methyladenosine methyltransferase complex, using the albumin-Cre system. Mettl3 liver-specific knockout mice and their wild-type littermates were subjected to 2/3 partial hepatectomy. Transcriptomic changes in liver tissue at 48 h after partial hepatectomy were detected by RNA-seq. Immunohistochemistry and immunofluorescence were used to determine protein expression levels of Ki67, hepatocyte nuclear factor 4 alpha, and cytokeratin 19. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling was also performed. Liver weight/body weight ratios after partial hepatectomy were significantly lower in Mettl3 liver-specific knockout mice than in wild-type mice at 48 h after 2/3 partial hepatectomy (3.1% ± 0.11% vs. 2.7% ± 0.03%). Compared with wild-type littermates, Mettl3 liver-specific knockout mice showed reduced bromodeoxyuridine staining and reduced Ki-67 expression at 48 h after 2/3 partial hepatectomy. RNA-seq analysis showed that Mettl3 liver-specific knockout delayed the cell cycle progression in murine liver by downregulating the expression levels of genes encoding cyclins D1, A2, B1, and B2. Loss of Mettl3-mediated N6-methyladenosine function led to attenuated liver regeneration by altering the mRNA decay of suppressor of cytokine signaling 6, thereby inhibiting the phosphorylation of signal transducer and activator of transcription 3 during early liver regeneration. These results demonstrated the importance of N6-methyladenosine mRNA modification in liver regeneration and suggest that Mettl3 targeting might facilitate liver regeneration.

SOCS family genes are a class of repressors in various signaling pathways of mammals involved in regulating immunity, growth, and development, but the information remains limited in teleost. The full-length cDNA sequence of the Japanese eel SOCS6 gene, named Aj SOCS6, was first cloned and showed to encode 529 amino acids with a conserved SH2 structural domain and a typical structure of a C-terminal SOCS box. Aj SOCS6 is evolutionarily close to that of rainbow trout and zebrafish. Aj SOCS6 gene expression was observed across all tissues in Japanese eel, with the highest levels found in the intestine. In vivo studies showed that Aj SOCS6 was significantly upregulated in the liver following exposure to LPS, poly I:C, and Aeromonas hydrophila infection. In vitro , stimulation with poly I:C, CpG, and A. hydrophila infection increased Aj SOCS6 expression in Japanese eel liver cells. Subcellular localization revealed that Aj SOCS6 was dispersed in the cytoplasm. Overexpressing Aj SOCS6 significantly suppressed the expression of immune-related genes, such as c-Rel and p65 in the NF-κB pathway, IFN1, IFN2, and IFN4 in the type I IFN signaling pathway, and the downstream inflammatory factor IL-6 in Japanese eel liver cells. Conversely, knocking down Aj SOCS6 in vitro in liver cells and in vivo in the liver, spleen, and kidney significantly upregulated these gene expressions. Co-transfection of Aj SOCS6 with Aj MyD88 into HEK293 cells significantly reduced NF-κB luciferase activities compared to Aj MyD88 single-transfection groups, in a natural state and under LPS stimulation. These findings suggest that Aj SOCS6 negatively regulates MyD88-dependent NF-κB and type I IFN signaling pathways, underscoring its role in the immune defense of fish against viral and bacterial infections. • The role of Aj SOCS6 in the signaling immune-related pathways was first studied in teleost. • Aj SOCS6 overexpression significantly reduced immune-related gene expression in the NF-κB and type I IFN pathways. • Aj SOCS6 effectively inhibited the MyD88-dependent NF-κB signaling pathway under LPS stimulation. [ABSTRACT FROM AUTHOR]

Objective: Lung cancer (LC) remains a threatening health issue worldwide. Methyltransferase-like protein 3 (METTL3) is imperative in carcinogenesis via m6A modification of microRNAs (miRNAs). This study estimated the effect of METTL3 in LC by regulating m6A methylation-mediated pri-miR-663 processing. Methods: miR-663 expression in 4 LC cell lines and normal HBE cells was determined using RT-qPCR. A549 and PC9 LC cells selected for in vitro studies were transfected with miR-663 mimics or inhibitor. Cell viability, migration, invasion, proliferation, and apoptosis were detected by CCK-8, Transwell, EdU, and flow cytometry assays. The downstream target genes and binding sites of miR-663 were predicted via Starbase database and validated by dual-luciferase assay. LC cells were delivered with oe-METTL3/sh-METTL3. Crosslinking between METTL3 and DGCR8 was verified by co-immunoprecipitation. Levels of m6A, miR-663, and pri-miR-663 were measured by m6A dot blot assay and RT-qPCR. m6A modification of pri-miR-663 was verified by Me-RIP assay. Finally, the effects of METTL3 in vivo were ascertained by tumor xenograft in nude mice. Results: miR-663 was upregulated in LC cells, and miR-663 overexpression promoted cell proliferation, migration, invasion, and inhibited apoptosis, but miR-663 knockdown exerted the opposite effects. miR-663 repressed SOCS6 expression. SOCS6 overexpression annulled the promotion of miR-663 on LC cell growth. METTL3 bound to DGCR8, and METTL3 silencing elevated the levels of pri-miR-663 and m6A methylation-modified pri-miR-663, and suppressed miR-663 maturation and miR-663 expression. METTL3 facilitated tumor growth in mice through the miR-663/SOCS6 axis. Conclusion: METTL3 promotes LC progression by accelerating m6A methylation-mediated pri-miR-663 processing and repressing SOCS6. [ABSTRACT FROM AUTHOR]

The objective of this study is to investigate lncRNA FLG-AS1-mediated miR-380-3p/SOCS6 axis in inflammation, oxidative stress, and apoptosis of retinal epithelial cells in diabetic retinopathy (DR). Fasting blood was collected from 60 DR patients and 60 healthy controls. The Pearson correlation was used to analyze the correlation between the expression levels of FLG-AS1 and miR-380-3p in DR patients. qRT-PCR and/or Western blotting were used to detect the expression of FLG-AS1, miR-380-3p, and SOCS6. After gain of function of FLG-AS1 or SOCS6 or loss of function of miR-380-3p, high glucose (HG)–treated human retinal pigment epithelial ARPE-19 cells were subjected to TUNEL assessment of apoptosis. ELISA was performed to detect the expression levels of IL-1β, IL-6, and TNF-α in cell culture supernatant. DCFH-DA was used to detect the level of ROS in the cells. MDA and SOD assay kits were used to measure the activity of MDA and SOD in the cells. Dual-luciferase reporter assay was performed to verify the binding between miR-380-3p and FLG-AS1 or between miR-380-3p and SOCS6. Streptozotocin injections were used to induce diabetes in rats which were injected with FLG-AS1 overexpression lentiviral vectors in the eye. Twenty weeks later, retinal tissue was isolated and stained with hematoxylin–eosin or TUNEL. Compared to that in healthy controls, FLG-AS1 expression decreased 2.5-fold and miR-380-3p expression increased 2.6-fold in the serum of DR patients. The expression levels of FLG-AS1 and miR-380-3p were negatively correlated in DR patients (r = −0.3772, P = 0.003). Overexpression of FLG-AS1 reduced inflammation, oxidative stress, and apoptosis of HG-treated ARPE-19 cells and alleviated retinal injury in diabetic rats. FLG-AS1 promoted the expression of SOCS6 by targeting miR-380-3p. Inhibition of miR-380-3p or overexpression of SOCS6 reduced inflammation, oxidative stress, and apoptosis of HG-treated ARPE-19 cells. FLG-AS1 mitigates DR by regulating retinal epithelial cell inflammation, oxidative stress, and apoptosis via the miR-380-3p/SOCS6 axis. [ABSTRACT FROM AUTHOR]

Abstract Background Many studies reporting that down-regulation of SOCS6 plays vital roles in promoting progression of malignant tumors have been published. The present study was performed to evaluate whether SOCS6 was significantly associated with prognosis of GIST patients. Methods Immunohistochemical staining was accomplished to evaluate the expression levels of SOCS6 among GIST patients. The impacts of SOCS6 expression on overall survival (OS) and recurrence-free survival (RFS) of GIST patients were assessed by Cox proportional hazard regression model analysis and Kaplan-Meier curve analysis. Results It was demonstrated that the expression level of SOCS6 was significantly associated with tumor size (P=0.001). Then according to Kaplan-Meier curve analysis, low expression of SOCS6 was significantly correlated with worse OS and RFS of GIST patients. Ultimately, it was revealed by Cox proportional regression model analysis that low expression of SOCS6 was an independent predictive factor for OS and RFS. Conclusions Low expression of SOCS6 was an independent prognostic factor for GIST, suggesting its potential as a novel biomarker predicting survival of GIST patients.

Numerous microRNAs (miRNAs) have been found to have an aberrant expression in the peripheral blood or psoriasis patients' lesions. Psoriasis was shown to have the abnormal expression of microRNA-203 (miR-203). It is a skin-specific signal that governs cellular proliferation in a protein kinase C-dependent manner and is mostly generated by keratinocytes. This work evaluated the expression levels of the circulating miR-203 target genes SOCS3, SOCS6, TP63, TNF-, IL8, and IL24 in psoriasis patients. Using a relative quantitation PCR technique, we determined the expression levels of miR-203 and its target genes (SOCS3, SOCS6, TP63, TNF-, IL8, and IL24) in the plasma of 120 psoriatic patients and matched healthy controls. The disease characteristics of the patients were then correlated with the expression results. We also conducted numerous enrichment analyses for the diseases, functions, and pathways connected to the under-researched biomarkers. Compared to healthy controls, psoriatic patients had significantly increased levels of miR-203 expression; 7.1 (4.4–9.9). In contrast, psoriatic patients had significantly lower expression of all the examined genes compared to healthy controls. Regarding all the study biomarkers, the receiver operating characteristic (ROC) curve analysis demonstrated significant sensitivity and specificity for differentiating between psoriatic patients and healthy controls. According to the results of the disease matching score generated by miR-203 and its target genes, psoriasis was ranked first with a score of 4.45. The third-place finisher with a value of 3.98, it also demonstrated that miR-203 and its target genes are connected to various skin disorders. Our results show that miR-203 contributes to psoriasis pathogenesis not only locally in skin lesions but also in circulation, indicating that it may contribute to the systemic symptoms of the illness. MiR-203 overexpression in psoriasis suggests that miR-203 may be involved in an anti-inflammatory response because it targets both SOCS gene family members and pro-inflammatory cytokines.

Periodontitis is a prevalent chronic inflammatory disease. Circular RNAs (circRNAs) have been revealed to play roles in the inflammatory response. Hence, this work aimed to explore the role and mechanism of circ_0062491 in periodontitis progression. Human periodontal ligament cells (PDLCs) were isolated from the periodontal ligament (PDL) of the healthy teeth with orthodontic requirement after tooth extraction. In vitro experiments were conducted by cell counting Kit-8 (CCK-8) assay, flow cytometry, Western blot, and ELISA to determine cell viability, apoptosis, and inflammatory response. The binding between miR-498 and circ_0062491 or SOCS6 was confirmed using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Circ_0062491 expression was decreased in periodontitis and LPS-induced PDLCs. Restoration of circ_0062491 attenuated LPS-induced apoptosis and inflammation in PDLCs in vitro. Mechanistically, circ_0062491 functioned as a sponge for miR-498, and miR-498 directly targeted SOCS6. Rescue experiments showed that miR-498 up-regulation reversed the protective action of circ_0062491 on PDLCs under LPS treatment. Moreover, silencing of miR-498 protected PDLCs from LPS-induced apoptosis and inflammation, which were abolished by SOCS6 knockdown. Circ_0062491 protected PDLCs from LPS-induced apoptosis and inflammation, suggesting a new target for the amelioration of periodontitis patients. [ABSTRACT FROM AUTHOR]

The suppressor of cytokine signaling 6 (SOCS6), an emerged important member of SOCS family, has attracted enhancing attention regarding its pivotal role in the development and progression of cancers. As part of negative feedback regulation, SOCS6 has been implicated in attenuating cytokine signal transduction via inhibiting the signaling cascade of activated cytokine receptors and multiple receptor tyrosine kinase signaling. Decreased SOCS6 expression is involved in diverse tumorigenic processes, such as abnormal cell proliferation, evasion of apoptosis, cancer migration, and cancer stem cell maintenance. Herein, this review summarized the mechanisms of SOCS6 regulation underlying multiple pathways. In particular, we focus on the pathological processes of cancer targeted by SOCS6 and discuss its inhibitory role during tumor progression. Also, we focused on the clinical relevance of SOCS6 in cancer biomarker and prognosis, as well as its significance in chemoresistance and radioresistance. In all, this review pave a way to assist in experimental designs and emphasize the potential clinical value of SOCS6 for cancer. [Display omitted] • SOCS6 prominently involves in inhibition of receptor tyrosine kinase signaling cascades. • SOCS6 overexpression participates in in cancer development, such as cell proliferation, apoptosis, and migration. • Reduced SOCS6 expression contributes to the tumorigenesis in in cancer of digestive, respiratory and hematological system. • SOCS6 overexpression may reverse the resistance of cancer cells to chemotherapy drugs or radiotherapy. • SOCS6 downregulation acts as independent prognostic factor of shorter OS and DFS in numerous cancer types. [ABSTRACT FROM AUTHOR]

Abstract Background Radiotherapy is a major treatment for esophageal squamous cell carcinoma (ESCC). However, HPV infection related radioresistance caused poor prognosis of ESCC. The function of SOCS6, which has been shown to be a tumor suppressor in several cancers, has not been fully investigated up till now. In this manuscript, we aim to further investigate the role of SOCS6 in regulating ESCC radioresistance. Methods Fifty-seven ESCC patients were enrolled for survival analysis. SOCS6 was stably overexpressed in HPV+ ESCC and ESCC cells, and cells were treated with radiation and then subjected to colony formation assays. Expression of DNA damage repair regulating proteins were examined by Western blotting. Cell growth, cell migration and cisplatin sensitivity were then analyzed. Sphere formation assays and flow cytometry were used to investigate changes in cancer stem cell (CSC) properties. Immunofluorescent staining and confocal microscopy were used to locate SOCS6 and c-Kit. Ubiquitylation level of c-Kit were analyzed after immunoprecipitation. Then, coimmunoprecipitation (CoIP) of SOCS6 and c-Kit were performed. In vivo, xenograft animal models were treated with radiation to examine the radiosensitivity. Results SOCS6 is correlated with better prognosis in ESCC patients. Radioresistance is impaired by SOCS6 upregulation, which inhibited cell growth, migration and increased sensitivity to cisplatin. SOCS6 significantly decreased the population of CSCs expressing the surface biomarker CD271 or CD24low/CD44high and their ability of sphere formation. SOCS6 and c-Kit were collocated in the cytoplasm. Blotting of ubiquitin and CoIP experiments indicated that the mechanism was related to ubiquitylation and degradation of the receptor c-Kit. Xenograft tumor mouse model showed that SOCS6 inhibited tumor growth and promoted radiosensitivity in vivo. Conclusions Our findings suggest that SOCS6 can promote the radiosensitivity of HPV+ ESCC and ESCC cells and reduce their stemness via ubiquitylation and degradation of c-Kit. Thus, SOCS6 is a potential target for overcoming radioresistance of ESCC.

Background: Many studies reporting that down-regulation of SOCS6 plays vital roles in promoting progression of malignant tumors have been published. The present study was performed to evaluate whether SOCS6 was significantly associated with prognosis of GIST patients. Methods: Immunohistochemical staining was accomplished to evaluate the expression levels of SOCS6 among GIST patients. The impacts of SOCS6 expression on overall survival (OS) and recurrence-free survival (RFS) of GIST patients were assessed by Cox proportional hazard regression model analysis and Kaplan-Meier curve analysis. Results: It was demonstrated that the expression level of SOCS6 was significantly associated with tumor size (P=0.001). Then according to Kaplan-Meier curve analysis, low expression of SOCS6 was significantly correlated with worse OS and RFS of GIST patients. Ultimately, it was revealed by Cox proportional regression model analysis that low expression of SOCS6 was an independent predictive factor for OS and RFS. Conclusions: Low expression of SOCS6 was an independent prognostic factor for GIST, suggesting its potential as a novel biomarker predicting survival of GIST patients. [ABSTRACT FROM AUTHOR]

Periodontitis is a common chronic inflammation that often occurs in adults. Circular RNAs (circRNAs) play a vital role in inflammation-related diseases. However, the role and potential basis of hsa_circ_0085289 in periodontitis remain unknown. Periodontal ligament cells (PDLCs) were exposed to lipopolysaccharide (LPS) to mimic periodontitis. The levels of circ_0085289, let-7f-5p, and suppressor of cytokine signaling 6 (SOCS6) were determined using qRT-PCR and western blot. The release of inflammatory cytokines was measured via enzyme-linked immunosorbent assay (ELISA). Cell viability and apoptosis were determined using Cell Counting Kit-8, flow cytometry, Caspase-3 Assay Kit, and western blot assays. The association between let-7f-5p and circ_0085289/SOCS6 was validated via dual-luciferase reporter, RNA pull-down, and RIP assays. Circ_0085289 and SOCS6 levels were reduced, and let-7f-5p level was increased in periodontitis patients and LPS-treated PDLCs. LPS stimulation caused PDLC injury and circ_0085289 downregulation. Moreover, circ_0085289 upregulation or let-7f-5p downregulation diminished LPS-triggered PDLC injury. Besides, circ_0085289 promoted SOCS6 expression by absorbing let-7f-5p. Circ_0085289 alleviated LPS-stimulated PDLC injury via targeting let-7f-5p. Moreover, let-7f-5p targeted SOCS6 to affect LPS-resulted PDLC injury. Circ_0085289 alleviated PDLC injury induced by LPS stimulation via modulating let-7f-5p/SOCS6 axis, suggesting a promising biomarker for periodontitis treatment. [ABSTRACT FROM AUTHOR]

Periodontitis refers to the inflammation of gums and the surrounding structures and caused by a bacterial infection. The infection occurs owing to poor oral hygiene and could destroy the bone and the gum over time if left untreated. The present study identified the involvement of a key long noncoding RNA (lncRNA), i.e. FGD5-AS1, in the pathogenesis of periodontitis by assessing its expression in the gingival tissues of patients diagnosed with chronic periodontitis (CP). Overexpression of FGD5-AS1 in primary human periodontal ligament cells (PDLCs) significantly reduced the lipopolysaccharide (LPS)-induced periodontitis, whereas its suppression aggravated this injury. Moreover, the miR-142-3p was markedly expressed in the gingival samples of patients diagnosed with CP and LPS-induced PDLCs. We found that the FGD5-AS1-mediated reduction in the inflammation was mediated through downside regulation of miR-142-3p, as evident from the upregulation of SOCS6, a target gene of miR-142-3p. Furthermore, the association between FGD5-AS1 and NF-κB pathway was detected. FGD5-AS1 was found to protect against LPS-stimulated PDLC injury through restraining the NF-κB signals. Based on these findings, we conclude that up-regulation of lncRNA FGD5-AS1 could protect against periodontitis via regulating the miR-142-3p/SOCS6/NF-κB signals. Therefore, the FGD5-AS1/miR-142-3p/SOCS6 axis may act as an important indicator in explaining the pathogenesis of periodontitis.

Jing Zhang,1,2 Xiong-Ming Pu,3 Yan Xiong41Postgraduate College of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2Department of Pathology, Affiliated Traditional Chinese Medicine Hospital, Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 3Department of Dermatology and Venereology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 4Department of Pathology, Peking University First Hospital, Beijing, People’s Republic of ChinaBackground: Kaposi’s sarcoma (KS) is a highly disseminated angiogenic tumour of endothelial cells. Many deregulated miRNAs, including kshv-mir-k12-1-5p, have been identified in KS. kshv-mir-k12-1-5p plays important roles in KS. However, the underlying mechanism is not fully understood. The aim of this study was to investigate the exact functions of kshv-mir-k12-1-5p in KS cells.Materials and methods: The biological functions of kshv-mir-k12-1-5p were studied using CCK-8, apoptosis, migration and invasion assays. Bioinformatics software was used to identify the target gene (SOCS6) of kshv-mir-k12-1-5p. A dual luciferase assay, Western blot (WB) and quantitative real-time polymerase chain reaction (q-PCR) were performed to further verify the target gene. The underlying molecular mechanisms of kshv-mir-k12-1-5p in KS cells were also explored.Results: kshv-mir-k12-1-5p can promote the proliferation, migration and invasion of KS cells and inhibit cell apoptosis. Suppressor of cytokine signalling 6 (SOCS6) was identified as a direct target of kshv-mir-k12-1-5p, and kshv-mir-k12-1-5p can downregulate SOCS6 expression. In addition, knockdown of SOCS6 rescued the effects of kshv-mir-k12-1-5p inhibitor. Hence, a direct relationship between kshv-mir-k12-1-5p and SOCS6 was confirmed.Conclusions: kshv-mir-k12-1-5p promotes the malignant phenotype of KS cells by targeting SOCS6, suggesting that kshv-mir-k12-1-5p could be a potential therapeutic target for KS.Keywords: kshv-mir-k12-1-5p, SOCS6, Kaposi’s sarcoma

MicroRNAs (miRNAs) are emerging as significant regulators of the tumorigenesis of gastric cancer (GC), and may be effective biomarkers for diagnosis, prognosis, and therapeutic targeting for GC. In this study, miR-653-5p was found to be significantly upregulated in GC tissues, serum, and cell lines and was strongly associated with poor prognosis in patients with GC. Furthermore, miR-653-5p promoted GC cell proliferation and metastasis in vivo and in vitro. Suppressor of cytokine signaling 6 (SOCS6) was directly targeted by miR-653-5p, and SOCS6 attenuated miR-653-5p-mediated GC cell growth, migration, and invasion. In addition, SOCS6-mediated inactivation of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway was also reversed by the administration of miR-653-5p. The findings from this study support a novel regulatory axis between miR-653-5p, SOCS6, and JAK2/STAT3 that may be a target for diagnosis and therapeutic intervention for GC.

Background: Radiotherapy is a major treatment for esophageal squamous cell carcinoma (ESCC). However, HPV infection related radioresistance caused poor prognosis of ESCC. The function of SOCS6, which has been shown to be a tumor suppressor in several cancers, has not been fully investigated up till now. In this manuscript, we aim to further investigate the role of SOCS6 in regulating ESCC radioresistance. Methods: Fifty-seven ESCC patients were enrolled for survival analysis. SOCS6 was stably overexpressed in HPV+ ESCC and ESCC cells, and cells were treated with radiation and then subjected to colony formation assays. Expression of DNA damage repair regulating proteins were examined by Western blotting. Cell growth, cell migration and cisplatin sensitivity were then analyzed. Sphere formation assays and flow cytometry were used to investigate changes in cancer stem cell (CSC) properties. Immunofluorescent staining and confocal microscopy were used to locate SOCS6 and c-Kit. Ubiquitylation level of c-Kit were analyzed after immunoprecipitation. Then, coimmunoprecipitation (CoIP) of SOCS6 and c-Kit were performed. In vivo, xenograft animal models were treated with radiation to examine the radiosensitivity. Results: SOCS6 is correlated with better prognosis in ESCC patients. Radioresistance is impaired by SOCS6 upregulation, which inhibited cell growth, migration and increased sensitivity to cisplatin. SOCS6 significantly decreased the population of CSCs expressing the surface biomarker CD271 or CD24low/CD44high and their ability of sphere formation. SOCS6 and c-Kit were collocated in the cytoplasm. Blotting of ubiquitin and CoIP experiments indicated that the mechanism was related to ubiquitylation and degradation of the receptor c-Kit. Xenograft tumor mouse model showed that SOCS6 inhibited tumor growth and promoted radiosensitivity in vivo. Conclusions: Our findings suggest that SOCS6 can promote the radiosensitivity of HPV+ ESCC and ESCC cells and reduce their stemness via ubiquitylation and degradation of c-Kit. Thus, SOCS6 is a potential target for overcoming radioresistance of ESCC. [ABSTRACT FROM AUTHOR]

Background/Aims: Glioblastoma is the most common and aggressive brain tumor and carries a poor prognosis. Previously, we found that neurotensin receptor 1 (NTSR1) contributes to glioma progression, but the underlying mechanisms of NTSR1 in glioblastoma invasion remain to be clarified. The aim of this study was to investigate the molecular mechanisms of NTSR1 in glioblastoma invasion. Methods: Cell migration and invasion were evaluated using wound-healing and transwell assays. Cell proliferation was detected using CCK-8. The expression of NTSR1, Jun, and suppressor of cytokine signaling 6 (SOCS6) was detected using western blotting. The expression of miR-494 was detected by Quantitative real-time PCR. Chromatin immunoprecipitation assay was performed to examine the interaction between Jun and miR-494 promoter. Dual-luciferase reporter assay and western blotting were performed to identify the direct regulation of SOCS6 by miR-494. An orthotopic xenograft mouse model was conducted to assess tumor growth and invasion. Results: NTSR1 knockdown attenuated the invasion of glioblastoma cells. Jun was positively regulated by NTSR1, which promoted miR-494 expression through binding to miR-494 promoter. SOCS6 was confirmed as a direct target of miR-494, thus, NTSR1-induced miR-494 upregulation resulted in SOCS6 downregulation. Both miR-494 and SOCS6 were involved in the NTSR1-induced invasion of glioblastoma cells. In vivo, tumor invasion and growth were inhibited by NTSR1 knockdown, but were restored with miR-494 overexpression. Conclusion: NTSR1 knockdown inhibited glioblastoma invasion via the Jun/miR-494/SOCS6 axis.

• S. uberis infection caused disruption of amino acid metabolism and accelerated arginine depletion in cells. • The supplementation of L-arginine alleviated the inflammatory response and injury induced by S. uberis. • S. uberis infection induced miR155 expression by activating p65 to play a pro-inflammatory role. • L-arginine attenuates inflammation through downregulation miR155 expression. L-arginine, as an essential substance of the immune system, plays a vital role in innate immunity. MiR155, a multi-functional microRNA, has gained importance as a regulator of homeostasis in immune cells. However, the immunoregulatory mechanism between L-arginine and miR155 in bacterial infections is unknown. Here, we investigated the potential role of miR155 in inflammation and the molecular regulatory mechanisms of L-arginine in Streptococcus uberis (S. uberis) infections. And we observed that miR155 was up-regulated after infection, accompanying the depletion of L-arginine, leading to metabolic disorders of amino acids and severe tissue damage. Mechanically, the upregulated miR155 mediated by the p65 protein played a pro-inflammatory role by suppressing the suppressor of cytokine signaling 6 (SOCS6)-mediated p65 ubiquitination and degradation. This culminated in a violently inflammatory response and tissue damage. Interestingly, a significant anti-inflammatory effect was revealed in L-arginine supplementation by reducing miR155 production via inhibiting p65. This work firstly uncovers the pro-inflammatory role of miR155 and an anti-inflammatory mechanism of L-arginine in S.uberis infection with a mouse mastitis model. Collectively, we provide new insights and strategies for the prevention and control of this important pathogen, which is of great significance for ensuring human food health and safety. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is a lethal malignancy and its prognosis remains dismal. Thus, a deeper understanding of the mechanisms is needed to provide a new insight for new therapies. It has been reported that long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) was downregulated in OSCC tissues, however, its functional mechanism remains uncertain. Here, we found that the overexpression of MEG3 suppressed migration and promoted apoptosis in OSCC cell lines, while inhibition of MEG3 exhibited opposite effect. We also found that MEG3 could effectively sponge miR‐548d‐3p and decrease its expression level. Moreover, miR‐548d‐3p repressed the expression of SOCS5 and SOCS6 through binding their 3'UTR, thereby modulating the JAK–STAT signaling pathway and functioning as an oncogene in OSCC cells. Importantly, overexpression of MEG3 enhanced the expression of SOCS5 and SOCS6 to regulate JAK–STAT pathway, whereas miR‐548d‐3p overexpression decreased the effects of MEG3 on levels of SOCS5/SOCS6. Furthermore, upregulated expression of miR‐548d‐3p could abrogate the effect of MEG3 overexpression on migration and apoptosis in OSCC cell lines. In addition, the overexpression of MEG3 inhibited tumor migration and facilitated apoptosis in vivo. Together, our results revealed that MEG3 could modulate JAK–STAT pathway via miR‐548d‐3p/SOCS5/SOCS6 to suppresses migration and promote apoptosis in OSCC. Our research indexed a new functional mechanism of MEG3 in OSCC, and this mechanism may be a potential prognostic factor and therapeutic target. © 2019 IUBMB Life, 2019 [ABSTRACT FROM AUTHOR]

Background/Aims: An increasing number of studies show that microRNAs (miRNAs) play crucial roles in nasopharyngeal carcinoma (NPC) tumorigenesis. The aim of our study was to investigate the biological roles and mechanisms of miR-142-3p in NPC. Methods: miR-142-3p expression was examined in NPC specimens and nasopharyngitis biopsy samples by quantitative real-time PCR. The biological functions of miR-142-3p were studied using a series of in vitro and in vivo approaches. Results: miR-142-3p is over-expressed in NPC tissues and cell lines. Knockdown of miR-142-3p significantly inhibited cell proliferation and cell cycle progression in vitro, and suppressed tumor growth in a mouse model. Suppressor of cytokine signaling 6 (SOCS6) was identified as a direct target of miR-142-3p, and miR-142-3p down-regulated the expression of SOCS6 by directly binding to its 3′untranslated region (UTR). Knockdown of SOCS6 abrogated the effects of miR-142-3p down-regulation. Conclusion: These findings indicate that miR-142-3p regulates NPC development by down-regulating SOCS6 expression and suggest that modulation of miR-142-3p expression could be a therapeutic strategy for NPC.

Background/Aims: Colorectal cancer (CRC) is one of the most common malignancies worldwide, and microRNAs play a crucial role in CRC biology. The purpose of this study was to investigate the exact functions and potential mechanisms of action of miR-301a in CRC. Methods: Quantitative real-time PCR was conducted to assess the expression of miR-301a. Cell proliferation was detected using MTT and colony formation assay, and cell invasion and migration were evaluated using Transwell assay. Luciferase reporter assay was used to identify the direct regulation of suppressor of cytokine signaling 6 (SOCS6) by miR-301a. Results: We first confirmed the upregulation of miR-301a in CRC tissues and cell lines. Gain-of-function and loss-of-function studies in the human CRC cell lines, SW480 and SW620, showed that miR-301a acts as an oncogene by increasing cell proliferation, migration and invasion as well as tumor growth. Furthermore, SOCS6 was identified as a target gene of miR-301a. Reintroduction of SOCS6 partially abrogated miR-301a-induced cell proliferation, migration and invasion. Conclusion: These data suggest that miR-301a promotes CRC progression by directly downregulating SOCS6 expression, and miR-301a may represent a novel biomarker for the prevention and treatment of CRC.

Background/Aims: Glioblastoma is the most common and aggressive brain tumor and carries a poor prognosis. Previously, we found that neurotensin receptor 1 (NTSR1) contributes to glioma progression, but the underlying mechanisms of NTSR1 in glioblastoma invasion remain to be clarified. The aim of this study was to investigate the molecular mechanisms of NTSR1 in glioblastoma invasion. Methods: Cell migration and invasion were evaluated using wound-healing and transwell assays. Cell proliferation was detected using CCK-8. The expression of NTSR1, Jun, and suppressor of cytokine signaling 6 (SOCS6) was detected using western blotting. The expression of miR-494 was detected by Quantitative real-time PCR. Chromatin immunoprecipitation assay was performed to examine the interaction between Jun and miR-494 promoter. Dual-luciferase reporter assay and western blotting were performed to identify the direct regulation of SOCS6 by miR-494. An orthotopic xenograft mouse model was conducted to assess tumor growth and invasion. Results: NTSR1 knockdown attenuated the invasion of glioblastoma cells. Jun was positively regulated by NTSR1, which promoted miR-494 expression through binding to miR-494 promoter. SOCS6 was confirmed as a direct target of miR-494, thus, NTSR1-induced miR-494 upregulation resulted in SOCS6 downregulation. Both miR-494 and SOCS6 were involved in the NTSR1-induced invasion of glioblastoma cells. In vivo, tumor invasion and growth were inhibited by NTSR1 knockdown, but were restored with miR-494 overexpression. Conclusion: NTSR1 knockdown inhibited glioblastoma invasion via the Jun/miR-494/SOCS6 axis. [ABSTRACT FROM AUTHOR]

Hypothalamic leptin receptor (LR) signaling regulates body weight by balancing food intake and energy expenditure. It is well established that the human LR undergoes ectodomain shedding, but little is known about the fate of the remaining cytosolic domain. This study demonstrates that regulated intramembrane proteolysis (RIP) releases the LR intracellular domain (LR ICD), which translocates to the mitochondria where it binds to SOCS6. This LR ICD-SOCS6 interaction stabilizes both proteins on the mitochondrial outer membrane and requires a functional BC box in SOCS6 for mitochondrial association and a central motif in the LR ICD for SOCS6 binding. The LR ICD prevents CCCP-induced mitochondrial depolarization and mitophagy as shown by lowered Parkin translocation and p62 accumulation. Strict regulation of mitochondrial dynamics in the hypothalamus is known to be essential for body weight homeostasis. This is the first study showing that the LR can directly modulate mitochondrial biology. [ABSTRACT FROM AUTHOR]

The SOCS (Suppressor of cytokine signaling) family members are a potential negative regulator of cytokine signaling pathway and play a key role to maintain immunological functions in animals. SOCS-6 is an important member of the SOCS family, however the functions of this gene have rarely been explored among eukaryotes. Herein, we cloned and expressed SOCS-6 gene from Bombyx mori (Dazao) (BmSOCS-6), and anti-rabbit antibodies were prepared using purified recombinant BmSOCS-6 protein. Under normal physiological conditions, the BmSOCS-6 expression was observed at varied levels in six tissues, with most greatly expressed in fat body and hemocytes. After immune challenge with viral, fungal and bacterial pathogens, the BmSOCS-6 showed distinctly varied expression patterns in tissue, time and microbe dependent manner. By contrast, recombinant BmSOCS-6 protein strongly enhanced the expression of epidermal growth factor receptor (EGFR) pathway related genes, while the depletion of BmSOCS-6 by double stranded RNA suppressed their production. Altogether we concluded that BmSOCS-6 may improve the efficiency of EGFR signaling pathway in B. mori (Dazao). [ABSTRACT FROM AUTHOR]

microRNAs (miRNAs) play critical roles in cancer development and progression. This study investigated the effects of miR-19 in human osteosarcoma (OS) development. Here, we showed that miR-19 was frequently upregulated in OS tissues and cell lines. Moreover the expression of miR-19 was associated with TNM stage, metastasis, size and poor overall survival. Mechanistically, miR-19 dramatically suppressed OS growth in vitro and in vivo. Bioinformatics analyses predicted that SOCS6 is a potential target gene of miR-19 in OS, which was confirmed by luciferase-reporter assay. We also found that SOCS6 expression was downregulated and negatively correlated with miR-19 expression in OS tissues clinically. Moreover, ectopic SOCS6 could reverse miR-19 induced OS growth. Finally, JAK2/STAT3 signaling pathway involves miR-19/SOCS6-mediated OS progression. Together, our data provide important evidence for miR-19 mediated SOCS6 in OS growth and revealed miR-19/SOCS6/JAK2/STAT3 pathway as a potential therapeutic strategy for OS patients. [ABSTRACT FROM AUTHOR]

Background: Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus (DM). A recent in vitro study found that the suppressor of cytokine signaling 6 (SOCS6) plays a protective role in DR and DM. However, to date, no clinical studies have focused on the role of SOSC6 in DR development., Objectives: The present study aimed to investigate the expression and clinical significance of serum SOCS6 in DR., Material and Methods: A total of 159 DR patients were enrolled in the study. Additionally, 156 type 2 DM (T2DM) patients without DR were recruited as controls. Serum levels of SOCS6, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), vascular endothelial growth factor (VEGF), and angiopoietin-2 (ANG-2) were measured using enzyme-linked immunosorbent assay (ELISA). Demographic and clinical data were collected., Results: Age, the course of DM, systolic blood pressure (SBP), diastolic blood pressure (DBP), and the levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were significantly higher in proliferative DR (PDR) patients. Serum SOCS6 levels in PDR patients were remarkably lower than in non-PDR patients or non-DR T2DM patients. The Pearson's analysis showed that SOCS6 was negatively correlated with CRP, IL-6, TNF-α, IL-1β, VEGF, and ANG-2. The serum levels of CRP, IL-6, TNF-α, IL-1β, VEGF, and ANG-2 in the SOCS6 low expression group were significantly increased compared to patients with high SOCS6 levels. Receiver operating characteristic (ROC) curves showed that SOCS6 could be a potential diagnostic biomarker for DR. For logistic regression, 3 models were used. It was found that SOCS6, the course of DM, SBP and DBP in model 1, IL-1β and TNF-α in model 2, and VEGF and ANG-2 in model 3 were risk factors for DR., Conclusions: The SOCS6 is decreased in DR patients and is related to severity and clinical outcomes, including inflammatory and angiogenic factors.

Background: Exosomes derived from oral squamous cell carcinoma (OSCC) could modulate OSCC development. This study aimed to explore effects of exosome-mediated lncRNA PART1 on OSCC cells., Methods: This study was performed in Tianjin Medical University Cancer Institute from February 2021 to March 2022. Bioinformatic analysis was performed on the public database GEPIA (http://gepia.cancer-pku.cn/). Exosomes isolated from cell lines squamous cell carcinoma 9 (SCC9) and Centre Antoine Lacassagne-27 (CAL27) were identified by transmission electron microscope and western blot. Exosome-mediated lncRNA PART1, microRNA-17-5p(miR-17-5p) and suppressor of cytokine signaling 6(SOCS6) RNA expressions were assessed by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Cell counting kit8(CCK-8), caspase-3 activity, and flow cytometry were applied to evaluate OSCC cell viabilities and apoptosis. Meanwhile, OSCC cell migratory ability and invasiveness were evaluated using transwell assay. Bindings between miR-17-5p and lncRNA PART1 or SOCS6 were validated using the luciferase reporter test. Western blot was used for detecting the protein levels of SOCS6, phosphorylated signal transducer and activator of transcription 3 (STAT3) and STAT3., Results: : According to GEPIA, lncRNA PART1 was downregulated in OSCC tissue samples and cells, and it had a positive correlation with the good prognosis of Head and neck squamous cell cancer (HNSCC) patients. After the exosomes from OSCC cells were isolated and verified, PART1 was then confirmed to be secreted by exosomes. Further, overexpression of exosome-mediated lncRNA PART1 inhibited OSCC cell viabilities, migration, and invasiveness but facilitated OSCC cell apoptosis. PART1 upregulated SOCS6 through sponging miR-17-5p. Moreover, exosome-mediated lncRNA PART1 suppressed the phosphorylation of STAT3., Discussion: Exosome-mediated lncRNA PART1 could mediate the OSCC progression via miR-17-5p/SOCS6 axis in vitro, suggesting that lncRNA PART1 might be a target for treating OSCC.

OBJECTIVE: Both miR-21 and miR-183 are upregulated in hepatocellular carcinoma (HCC) and are considered as oncomiR. However, their oncogenic roles are still not fully understood. This study aimed to explore the regulative role of miR-21 and miR-183 over suppressors of cytokine signaling 6 (SOCS6), a negative regulator of cytokine receptor signaling. MATERIALS AND METHODS: qRT-PCR analysis was performed to assess miR-21 and miR-183 expression in tumor tissues obtained from HCC patients and in HCC cell lines HepG2 and Hep3B. Their regulation over SOCS6 is verified using dual luciferase assay and Western blot analysis. The function of miR-21/miR-183-SOCS6 axis in cell growth, invasion and apoptosis was studied. RESULTS: MiR-21 and miR-183 expression in HCC tissues than in adjacent normal tissues. Knockdown of miR-21 and miR-183 in HepG2 and Hep3B cells could decrease cell viability, increase cell apoptosis and decrease cell invasion. Based on the dual luciferase assay and Western blot analysis, we confirmed that both miR-21 and miR-183 can simultaneously target SOCS6 and modulate its expression at protein level. Overexpression of SOCS6 without 3'UTR could significantly lower cell growth rate and invasion capability, but increase relative cas- pase 3/7 activity and the ratio of apoptotic cells. However, these effects could not be blocked by miR-21 or miR-183 mimics. CONCLUSIONS: This study revealed a novel miR-21/miR-183-SOCS6 axis that might play an important role in modulating cell growth and invasion of HCC cells. [ABSTRACT FROM AUTHOR]

Background/Aims: An increasing number of studies show that microRNAs (miRNAs) play crucial roles in nasopharyngeal carcinoma (NPC) tumorigenesis. The aim of our study was to investigate the biological roles and mechanisms of miR-142-3p in NPC. Methods: miR- 142-3p expression was examined in NPC specimens and nasopharyngitis biopsy samples by quantitative real-time PCR. The biological functions of miR-142-3p were studied using a series of in vitro and in vivo approaches. Results: miR-142-3p is over-expressed in NPC tissues and cell lines. Knockdown of miR-142-3p significantly inhibited cell proliferation and cell cycle progression in vitro, and suppressed tumor growth in a mouse model. Suppressor of cytokine signaling 6 (SOCS6) was identified as a direct target of miR-142-3p, and miR- 142-3p down-regulated the expression of SOCS6 by directly binding to its 3'untranslated region (UTR). Knockdown of SOCS6 abrogated the effects of miR-142-3p down-regulation. Conclusion: These findings indicate that miR-142-3p regulates NPC development by downregulating SOCS6 expression and suggest that modulation of miR-142-3p expression could be a therapeutic strategy for NPC. [ABSTRACT FROM AUTHOR]

Background/Aims: Colorectal cancer (CRC) is one of the most common malignancies worldwide, and microRNAs play a crucial role in CRC biology. The purpose of this study was to investigate the exact functions and potential mechanisms of action of miR-301a in CRC. Methods: Quantitative real-time PCR was conducted to assess the expression of miR-301a. Cell proliferation was detected using MTT and colony formation assay, and cell invasion and migration were evaluated using Transwell assay. Luciferase reporter assay was used to identify the direct regulation of suppressor of cytokine signaling 6 (SOCS6) by miR-301a. Results: We first confirmed the upregulation of miR-301a in CRC tissues and cell lines. Gain-of-function and loss-of-function studies in the human CRC cell lines, SW480 and SW620, showed that miR-301a acts as an oncogene by increasing cell proliferation, migration and invasion as well as tumor growth. Furthermore, SOCS6 was identified as a target gene of miR-301a. Reintroduction of SOCS6 partially abrogated miR-301a-induced cell proliferation, migration and invasion. Conclusion: These data suggest that miR-301a promotes CRC progression by directly downregulating SOCS6 expression, and miR-301a may represent a novel biomarker for the prevention and treatment of CRC. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Receptor tyrosine kinases (RTKs) are a family of cell surface receptors that play critical roles in signal transduction from extracellular stimuli. Many in this family of kinases are overexpressed or mutated in human malignancies and thus became an attractive drug target for cancer treatment. The signaling mediated by RTKs must be tightly regulated by interacting proteins including protein-tyrosine phosphatases and ubiquitin ligases. The suppressors of cytokine signaling (SOCS) family proteins are well-known negative regulators of cytokine receptors signaling consisting of eight structurally similar proteins, SOCS1-7, and cytokine-inducible SH2-containing protein (CIS). A key feature of this family of proteins is the presence of an SH2 domain and a SOCS box. Recent studies suggest that SOCS proteins also play a role in RTK signaling. Activation of RTK results in transcriptional activation of SOCS-encoding genes. These proteins associate with RTKs through their SH2 domains and subsequently recruit the E3 ubiquitin machinery through the SOCS box, and thereby limit receptor stability by inducing ubiquitination. In a similar fashion, SOCS proteins negatively regulate mitogenic signaling by RTKs. It is also evident that RTKs can sometimes bypass SOCS regulation and SOCS proteins can even potentiate RTKs-mediated mitogenic signaling. Thus, apart from negative regulation of receptor signaling, SOCS proteins may also influence signaling in other ways. [ABSTRACT FROM AUTHOR]

Highlights: [•] miR-17-5p functions as a pro-proliferative miRNA in gastric cancer. [•] SOCS6 was demonstrated to be a direct target of miR-17-5p. [•] SOCS6 exerted an opposite function with miR-17-5p in gastric cancer. [•] miR-17-5p acts as a pro-proliferative factor by repressing SOCS6 in gastric cancer. [Copyright &y& Elsevier]