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Xue Bai,1,2,* LiTing Yang,1,2,* Ruxin Liu,1,2 YuJiao Tang,1,2 Long Yang,1,2 Lingna Ma,1,2 MengFei Chen,2 Ling Zhang2 1Department of Emergency, The Third Clinical Medical College of Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Emergency, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: MengFei Chen; Ling Zhang, Tel +86 13389513801 ; +86 13895318660, Email prayer_821@sina.com; zhangling_7015@sina.comObjective: Cellular pyroptosis is a pro-inflammatory mode of programmed cell death that has been identified in recent years, and studies have shown that the LncRNA SOX2OT regulates myocardial injury during sepsis, but the exact regulatory mechanism is unclear. The aim of this study was to assess the role of SOX2OT in regulating cardiomyocyte injury during sepsis cardiomyopathy.Methods: Rat cardiomyocytes, C57BL/6 mice, and transgenic mice were divided into four groups: control, LPS, LPS+ knockout LncRNA SOX2OT, and LPS+ overexpression LncRNA SOX2OT. Inflammatory factor levels were detected by qPCR. Associated proteins and gene expression were detected by Western blotting and qPCR. Dual luciferase was used to detect the target genes of SOX2OT. Nrf2 and EZH2 knockdown and overexpression cell lines were established, and the expression of related genes was detected by qPCR.Results: Results In this study, we found that SOX2OT knockdown exacerbated LPS-induced levels of inflammatory factors and procalcitoninogen (PCT), and increased the expression of pyroptosis-related proteins and LDH. The results of dual luciferase reporter gene assay showed that EZH2 is the target gene of SOX2OT, and overexpression of SOX2OT decreased the expression of EZH2; we also found that knockdown of EZH2 in H9c2 cells decreased the expression of Nrf2, which was positively correlated with the expression level of NLRP3. Further in vivo results showed that overexpression of SOX2OT attenuated SIMD (sepsis-induced myocardial dysfunction), as evidenced by improved myocardial structural integrity and reduced inflammatory cell infiltration. The expression of pyroptosis-related proteins and LDH was significantly increased in the mice in the LPS group; this effect was reversed by overexpression of SOX2OT, and potentiated by knockdown of SOX2OT.Conclusion: Our data reveal a novel mechanism by which SOX2OT inhibits cardiomyocyte sepsis through the EZH2/Nrf-2/NLRP3 pathway, thereby attenuating septic myocardial injury, which may contribute to the development of new therapeutic strategies.Keywords: SOX2OT, EZH2, Nrf2, sepsis, pyroptosis

Abstract Hormone receptor (HR)-positive breast cancer can become aggressive after developing hormone-treatment resistance. This study elucidated the role of long non-coding RNA (lncRNA) SOX2OT in tamoxifen-resistant (TAMR) breast cancer and its potential interplay with the tumor microenvironment (TME). TAMR breast cancer cell lines TAMR-V and TAMR-H were compared with the luminal type A cell line (MCF-7). LncRNA expression was assessed via next-generation sequencing, RNA extraction, lncRNA profiling, and quantitative RT-qPCR. SOX2OT overexpression effects on cell proliferation, migration, and invasion were evaluated using various assays. SOX2OT was consistently downregulated in TAMR cell lines and TAMR breast cancer tissue. Overexpression of SOX2OT in TAMR cells increased cell proliferation and cell invasion. However, SOX2OT overexpression did not significantly alter SOX2 levels, suggesting an independent interaction within TAMR cells. Kaplan–Meier plot analysis revealed an inverse relationship between SOX2OT expression and prognosis in luminal A and B breast cancers. Our findings highlight the potential role of SOX2OT in TAMR breast cancer progression. The downregulation of SOX2OT in TAMR breast cancer indicates its involvement in resistance mechanisms. Further studies should explore the intricate interactions between SOX2OT, SOX2, and TME in breast cancer subtypes.

Hormone receptor (HR)-positive breast cancer can become aggressive after developing hormone-treatment resistance. This study elucidated the role of long non-coding RNA (lncRNA) SOX2OT in tamoxifen-resistant (TAMR) breast cancer and its potential interplay with the tumor microenvironment (TME). TAMR breast cancer cell lines TAMR-V and TAMR-H were compared with the luminal type A cell line (MCF-7). LncRNA expression was assessed via next-generation sequencing, RNA extraction, lncRNA profiling, and quantitative RT-qPCR. SOX2OT overexpression effects on cell proliferation, migration, and invasion were evaluated using various assays. SOX2OT was consistently downregulated in TAMR cell lines and TAMR breast cancer tissue. Overexpression of SOX2OT in TAMR cells increased cell proliferation and cell invasion. However, SOX2OT overexpression did not significantly alter SOX2 levels, suggesting an independent interaction within TAMR cells. Kaplan–Meier plot analysis revealed an inverse relationship between SOX2OT expression and prognosis in luminal A and B breast cancers. Our findings highlight the potential role of SOX2OT in TAMR breast cancer progression. The downregulation of SOX2OT in TAMR breast cancer indicates its involvement in resistance mechanisms. Further studies should explore the intricate interactions between SOX2OT, SOX2, and TME in breast cancer subtypes. [ABSTRACT FROM AUTHOR]

Abstract Increasing evidence indicates the major role of mitochondrial function in neurodegenerative disease. However, it is unclear whether mitochondrial dynamics directly affect postoperative neurocognitive disorder (PND). This study aimed to analyze the underlying mechanisms of mitochondrial dynamics in the pathogenesis of PND. Tibial fracture surgery was performed in elderly mice to generate a PND model in vivo. Cognitive behavior was evaluated 3 days post-surgery using novel object recognition and fear conditioning. A gradual increase in the SOX2OT mRNA level and decrease in the SOX2 mRNA level were noted, with impaired cognitive function, in the mice 3 days after tibial surgery compared with mice in the sham group. To evaluate the role of SOX2OT in PND, SOX2OT knockdown was performed in vitro and in vivo using lentivirus transfection in HT22 cells and via brain stereotactic injection of lentivirus, respectively. SOX2OT knockdown reduced apoptosis, inhibited oxidative stress, suppressed mitochondrial hyperdivision, attenuated surgery-induced cognitive dysfunction, and promoted downstream SOX2 expression in elderly mice. Furthermore, Sox2 alleviated mitochondrial functional damage by inhibiting the transcription of mitochondrial division protein Drp1. Our study findings indicate that SOX2OT knockout alleviates surgery-induced mitochondrial fission and cognitive function defects by upregulating the expression of Sox2 in mice, resulting in the inhibition of drp1 transcription. Therefore, regulation of the SOX2/Drp1 pathway may be a potential mechanism for the treatment of patients with PND.

Increasing evidence indicates the major role of mitochondrial function in neurodegenerative disease. However, it is unclear whether mitochondrial dynamics directly affect postoperative neurocognitive disorder (PND). This study aimed to analyze the underlying mechanisms of mitochondrial dynamics in the pathogenesis of PND. Tibial fracture surgery was performed in elderly mice to generate a PND model in vivo. Cognitive behavior was evaluated 3 days post-surgery using novel object recognition and fear conditioning. A gradual increase in the SOX2OT mRNA level and decrease in the SOX2 mRNA level were noted, with impaired cognitive function, in the mice 3 days after tibial surgery compared with mice in the sham group. To evaluate the role of SOX2OT in PND, SOX2OT knockdown was performed in vitro and in vivo using lentivirus transfection in HT22 cells and via brain stereotactic injection of lentivirus, respectively. SOX2OT knockdown reduced apoptosis, inhibited oxidative stress, suppressed mitochondrial hyperdivision, attenuated surgery-induced cognitive dysfunction, and promoted downstream SOX2 expression in elderly mice. Furthermore, Sox2 alleviated mitochondrial functional damage by inhibiting the transcription of mitochondrial division protein Drp1. Our study findings indicate that SOX2OT knockout alleviates surgery-induced mitochondrial fission and cognitive function defects by upregulating the expression of Sox2 in mice, resulting in the inhibition of drp1 transcription. Therefore, regulation of the SOX2/Drp1 pathway may be a potential mechanism for the treatment of patients with PND. [ABSTRACT FROM AUTHOR]

Background: Renal tubular injury is the main feature of diabetic nephropathy (DN). We intend to investigate the function and related mechanisms of lncRNA SOX2 overlapping transcript (SOX2OT) in high glucose (HG)‐induced oxidative stress and apoptosis of renal tubular epithelial cells (RTECs). Methods: To construct diabetes models, the human kidney‐2 (HK‐2) cells were treated with HG (30 mM), and mice were injected with streptozotocin. The levels of intracellular and mitochondrial reactive oxygen species (ROS) were assessed by dihydroethidium staining and MitoSox staining. The cell apoptosis was assessed by flow cytometry and TUNEL staining. Levels of serum creatinine, blood urea nitrogen (BUN), Urinary ACR, and oxidative stress marker 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) were detected by relevant kits. In addition, fluorescence in situ hybridization staining, RNA‐pull down, RNA immunoprecipitation (RIP), co‐immunoprecipitation (co‐IP), dual‐luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) were also executed. Results: Levels of SOX2OT and silent information regulator 1 (SIRT1) were down‐regulated in HG‐cultured HK‐2 cells. Overexpressing SOX2OT reduced intracellular and mitochondrial ROS levels and cell apoptosis in vitro. Moreover, SOX2OT overexpression also reduced serum creatinine, BUN, urinary ACR, 8‐OHdG, renal tubular injury markers KIM1 and NGAL, ROS levels, and cell apoptosis in vivo. In addition, SOX2OT promoted SIRT1 expression by suppressing its ubiquitination. Besides, interference with SIRT1 reversed the inhibitory effect of SOX2OT overexpression on HG‐induced oxidative stress and apoptosis. Forkhead box A2 (Foxa2) levels were up‐regulated in HG‐cultured HK‐2 cells. Foxa2 could bind to the SOX2OT promoter and suppress its expression. Furthermore, interfering with SOX2OT reversed the inhibitory effect of Foxa2 interference on HG‐induced oxidative stress and apoptosis. Conclusion: Foxa2‐mediated SOX2OT up‐regulation reduced oxidative stress and apoptosis of RTECs by promoting SIRT1 expression, thus alleviating the progression of DN. Summary at a Glance: Renal tubule injury plays a major role in the progression of diabetic nephropathy (DN). This study explored the pathogenesis of DN from the perspective of renal tubular epithelial cell injury mediated by oxidative stress under the effect of high glucose (HG). Authors revealed that lncRNA SOX2OT was lowly expressed in renal tubular epithelial cells; Foxa2 was highly expressed in the DN mouse model and HG‐induced renal tubular epithelial cells; lncRNA SOX2OT promoted SIRT1 expression by suppressing its ubiquitination; Foxa2 could bind to the lncRNA SOX2OT promoter and suppress its expression; overexpression of lncRNA SOX2OT inhibits oxidative stress and apoptosis by up‐regulating the SIRT1 levels and improves renal function. [ABSTRACT FROM AUTHOR]

Background: SOX2OT is a novel cancer associated long non-coding RNA (LncRNA) with higher expression in variable tumor tissues, including esophageal squamous cell carcinoma (ESCC). It also plays an important function in embryonic neuronal development. Regarding its function in both stemness and carcinogenesis, here, we aimed to investigate its expression and function in tumorspheres of the esophagus using the RNAi method. Material & Methods: Two esophageal squamous cancer cells (ESCC): KYSE30 and YM1 cells were used for sphere enrichment. Cells were transfected with SOX2OT targeting and control siRNA. The size and the number of spheres were measured using light microscopy. Gene expression of the pluripotency genes was measured by qRT-PCR and docetaxel chemoresistance was assessed by MTS viability assay. Results: Our findings showed that ESCC tumorspheres overexpress SOX2OT gene along with other stemness genes (SOX2, OCT4A, and Nanog) compared to their original cancer cells. RNAi experiments indicated that SOX2OT knockdown can suppress the stemness-related gene expression, sphere formation ability (both size and number), and docetaxel resistance as three of the main cancer stem cell characteristics of tumorspheres. Conclusion: Altogether our results showed the regulatory role of SOX2OT in pluripotency and stemness in ESCC tumorspheres. Our results suggest a potential application of SOX2OT inhibition in combination with docetaxel for ESCC inhibition in vitro. [ABSTRACT FROM AUTHOR]

Guangqin Ran, Xiaofan Zhu, Yan Qin Department of Obstetrics and Gynecology, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, 401147, People’s Republic of ChinaCorrespondence: Yan QinDepartment of Obstetrics and Gynecology, Chongqing General Hospital, University of Chinese Academy of Sciences, No. 118, Xingguang Avenue, Liangjiang New Area, Chongqing, 401147, People’s Republic of ChinaTel +86 23-63390545Email yanqinchongqing@163.comPurpose: LncRNA SOX2OT plays protective roles in high glucose-induced injuries, suggesting its potential involvement in diabetes. Therefore, we analyzed the role of SOX2OT in gestational diabetes mellitus (GDM).Methods: A total of 216 pregnant women with a gestational age of about 2 months were enrolled in this study. The 216 pregnant women were monitored until delivery to record the occurrence of GDM. Adverse events, including miscarriage, premature delivery, intrauterine distress, intrauterine death, intrauterine infection, fetal malformation, macrosomia, and hypertension, were recorded.Results: Two hundred sixteen pregnant women were divided into high and low SOX2OT level groups (n=108), with the median plasma SOX2OT level on the day of admission as the cutoff value. It was observed that the incidence of GDM was higher in the high SOX2OT level group (40/108) than in the low SOX2OT level group (12/108). Moreover, the SOX2OT expression level was higher in GDM patients than in non-GDM participants, and ROC curve analysis showed that plasma SOX2OT levels on the day of admission could separate potential GDM patients from the rest participants. Importantly, higher incidences of miscarriage, premature delivery, intrauterine distress, intrauterine death, intrauterine infection, fetal malformation, macrosomia, and hypertension were observed in the high SOX2OT group compared to the low SOX2OT group.Conclusion: SOX2OT is highly expressed in GDM and is closely correlated with multiple adverse events.Keywords: gestational diabetes mellitus, SOX2OT, adverse events

Abstract Background Accumulating evidences have demonstrated that long non-coding RNAs (lncRNAs) are involved in the pathophysiology of diabetic nephropathy (DN). lncRNA SOX2OT plays an essential role in many diseases, including diabetes. Herein, we aim to investigate the underlying mechanism of lncRNA SOX2OT in DN pathogenesis. Methods Streptozotocin-induced DN mouse models and high glucose-induced mouse mesangial cells were constructed to examine the expression pattern of lncRNA SOX2OT. The activation of autophagy was evaluated using immunohistochemistry, immunofluorescence and western blot analysis, respectively. SOX2OT overexpressing plasmid was applied to further verify the functional role of SOX2OT in DN pathogenesis. CCK-8 and EDU assays were performed to the proliferation of mesangial cells. Additionally, rapamycin, the inhibitor of mTOR signaling, was used to further clarify whether SOX2OT controls DN development through Akt/mTOR pathway. Results lncRNA SOX2OT was markedly down-regulated both in streptozotocin-induced DN mice and high glucose-induced mouse mesangial cells. Moreover, overexpression of lncRNA SOX2OT was able to diminish the suppression of autophagy and alleviate DN-induced renal injury. Functionally, CCK-8 and EDU assays indicated that lncRNA SOX2OT overexpression significantly suppressed the proliferation and fibrosis of mesangial cells. Additionally, an obvious inhibition of Akt/mTOR was also observed with lncRNA SOX2OT overexpression, which was then further verified in vivo. Conclusion In summary, we demonstrated that lncRNA SOX2OT alleviates the pathogenesis of DN via regulating Akt/mTOR-mediated autophagy, which may provide a novel target for DN therapy.

Zhiyuan Wu,1,* Yongqin Yu,1,* Lanyan Fu,2 Hanran Mai,2 Li Huang,1 Di Che,2 Jianping Tao,1 Xiaoqiong Gu2– 4 1Department of Pediatric Intensive Care Unit, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, People’s Republic of China; 2Department of Clinical Biological Resource Bank, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, People’s Republic of China; 3Department of Blood Transfusion, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, People’s Republic of China; 4Department of Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoqiong Gu; Jianping Tao Email guxiaoqiong@gwcmc.org; golou6354@163.comBackground: Sepsis in children is one of the main causes of death in pediatric intensive care units (PICUs); however, the pathogenesis of sepsis is not fully clear. Previous studies revealed that many genetic variations were related to sepsis susceptibility. A long non-coding RNA SOX2 overlapping transcript (SOX2OT) may play a role in mitochondrial homeostasis and antioxidative activity, but the relationship between the lncRNA SOX2OT polymorphism and sepsis susceptibility has not been reported.Methods: In this study, 474 pediatric sepsis patients and 678 healthy controls were recruited from southern China. After genotyping, the strength of the associations was evaluated through odds ratios (ORs) and 95% confidence intervals (CIs).Results: The SOX2OT rs9839776 T allele was associated with decreased susceptibility to sepsis in southern Chinese children (TT/CT vs CC adjusted OR = 0.778, 95% CI = 0.610– 0.992; P = 0.0431). Moreover, the difference in susceptibility was greater in children of age > 60 months (adjusted OR = 0.458, 95% CI = 0.234– 0.896; P = 0.0225), survivors (adjusted OR = 0.758, 95% CI = 0.585– 0.972; P = 0.0358), males (adjusted OR = 0.655, 95% CI = 0.479– 0.894; P = 0.0077) and the sepsis subgroup (adjusted OR = 0.548, 95% CI = 0.343– 0.876; P = 0.0120).Conclusion: The rs9839776 T allele may contribute to decreased sepsis risk in Chinese children. Future studies with a larger sample size are needed to verify these results.Keywords: sepsis, SOX2OT, rs9839776, susceptibility, polymorphism

Abstract Background Aberrant hippocampal neurogenesis is an important pathological feature of sepsis-associated encephalopathy. In the current study, we examined the potential role of the long noncoding RNA (lncRNA) sex-determining region Y-box 2 (SOX2) overlapping transcript (SOX2OT), a known regulator of adult neurogenesis in sepsis-induced deficits in hippocampal neurogenesis and cognitive function. Methods Sepsis was induced in adult C57BL/6 J male mice by cecal ligation and perforation (CLP) surgery. Randomly selected CLP mice were transfected with short interfering RNAs (siRNAs) against SOX2OT or SOX2, or with scrambled control siRNA. Cognitive behavior was tested 8–12 days post-surgery using a Morris water maze. Western blotting and RT-qPCR were used to determine expression of SOX2, Ki67, doublecortin (DCX), nestin, brain lipid-binding protein, and glial fibrillary acidic protein (GFAP) in the hippocampus. The number of bromodeoxyuridine (BrdU)+/DCX+ cells, BrdU+/neuronal nuclei (NeuN)+ neurons, and BrdU+/GFAP+ glial cells in the dentate gyrus were assessed by immunofluorescence. Results CLP mice showed progressive increases in SOX2OT and SOX2 mRNA levels on days 3, 7, and 14 after CLP surgery, accompanied by impaired cognitive function. Sepsis led to decrease in all neuronal markers in the hippocampus, except GFAP. Immunofluorescence confirmed the decreased numbers of BrdU+/DCX+ cells and BrdU+/NeuN+ neurons, and increased numbers of BrdU+/GFAP+ cells. SOX2OT knockdown partially inhibited the effects of CLP on levels of SOX2 and neuronal markers, neuronal populations in the hippocampus, and cognitive function. SOX2 deficiency recapitulated the effects of SOX2OT knockdown. Conclusion SOX2OT knockdown improves sepsis-induced deficits in hippocampal neurogenesis and cognitive function by downregulating SOX2 in mice. Inhibiting SOX2OT/SOX2 signaling may be effective for treating or preventing neurodegeneration in sepsis-associated encephalopathy.

Abstract Background Accumulating evidence indicates that long non-coding RNAs (lncRNAs) are potential biomarkers and key regulators of tumour development and progression. SOX2 overlapping transcript (SOX2OT) is a novel lncRNA that acts as a potential biomarker and is involved in the development of cancer and cancer stem cells. However, the clinical significance and molecular mechanism of SOX2OT in bladder cancer are still unknown. Methods The expression level of SOX2OT was determined by RT-qPCR in a total of 106 patients with urothelial bladder cancer and in different bladder cancer cell (BCC) lines. Bladder cancer stem cells (BCSCs) were isolated from BCCs using flow cytometry based on the stem cell markers CD44 and ALDH1. Loss-of-function experiments were performed to investigate the biological roles of SOX2OT in the stemness phenotype of BCSCs. Comprehensive transcriptional analysis, RNA FISH, dual-luciferase reporter assays and western blots were performed to explore the molecular mechanisms underlying the functions of SOX2OT. Results SOX2OT was highly expressed in bladder cancer, and increased SOX2OT expression was positively correlated with a high histological grade, advanced TNM stage and poor prognosis. Further experiments demonstrated that knockdown of SOX2OT inhibited the stemness phenotype of BCSCs. Moreover, inhibition of SOX2OT delayed xenograft tumour growth and decreased metastases in vivo. Mechanistically, we found that SOX2OT was mainly distributed in the cytoplasm and positively regulated SOX2 expression by sponging miR-200c. Furthermore, SOX2 overexpression reversed the SOX2OT silencing-induced inhibition of the BCSC stemness phenotype. Conclusion This study is the first to demonstrate that SOX2OT plays an important regulatory role in BCSCs and that SOX2OT may serve as a potential diagnostic biomarker and therapeutic target in bladder cancer.

Sox2 overlapping transcript (Sox2ot) is a long non-coding RNA (lncRNA), which harbors one of the major regulators of pluripotency, the Sox2 gene, in its intronic region. Sox2ot is primarily expressed in the developing neuroepithelium. However, its role in neural tube closure and embryonic development remains unclear. To investigate if Sox2ot is required for neural tube closure and embryonic development, Sox2ot promoter was deleted by CRISPR-Cas9 genome editing technology to prevent Sox2ot gene expression in mice. We designed 9 guide RNAs to specifically target the Sox2ot promoter and 3 gRNAs induced gene editing on the promoter of the Sox2ot gene in cells transfected with Cas9 mRNA and gRNAs. Then, these gRNAs and Cas9 mRNA were injected into mouse zygotes and implanted into pseudopregnant mice. A Sox2ot promoter-deleted mouse line was identified with complete deletion of promoter as well as deletion of exon 1 and exon 2. Sox2ot transcript was truncated with a lack of exon 1 and exon 2 in Sox2ot promoter-deleted mice. Furthermore, neural tube closure and embryonic development were checked at E9.5, E10.5, E14.5, E17.5 and after-birth (P2) and we did not find any failure of neural tube closure and aberrant embryonic development in Sox2ot promoter-deleted mice. Thus, our study demonstrated that CRISPR-Cas9 gene editing in Sox2ot promoter leads to its truncated expression and does not influence neural tube closure and embryonic development. • CRISPR/Cas9 mediates gene editing on Sox2ot promoter in vitro and in vivo. • Sox2ot transcript is truncated in Sox2ot promoter-deleted mice. • Truncation of Sox2ot transcript does not affect neural tube closure and embryonic development. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) serve as crucial regulators in the pathogenesis of spinal cord injury (SCI). However, the role of lncRNA SOX2 overlapping transcript (SOX2OT) in SCI remains to be well revealed. An SCI rat model was established and assessed by the Basso–Beattie–Bresnahan (BBB) method. An SCI PC12 cell model was established through lipopolysaccharide (LPS) treatment. Quantitative real-time polymerase chain reaction assay was used for SOX2OT, miR-331-3p, and neurogenic differentiation 1 (Neurod1) mRNA levels. Cell counting kit-8 assay and flow cytometry analysis were performed for cell viability and apoptosis, respectively. Enzyme-linked immunosorbent assay was performed for the levels of inflammatory cytokines. The production of superoxide dismutase and malondialdehyde was determined with relevant kits. Dual-luciferase reporter and RNA immunoprecipitation assays were conducted for the relationships among SOX2OT, miR-331-3p, and Neurod1. Western blot assay was employed for protein levels. SOX2OT was elevated in SCI rat and cell models. SOX2OT knockdown relieved the injury of SCI in SCI rat model. Moreover, the suppressive role in PC12 cell viability and the promotional roles in apoptosis, inflammation, and oxidative stress mediated by LPS were all restored by silencing SOX2OT. For mechanism analysis, SOX2OT was identified as a sponge of miR-331-3p to positively regulate Neurod1 expression. Inhibition of miR-331-3p reversed the effect of SOX2OT knockdown on LPS-induced PC12 damage. Overexpression of miR-331-3p protected PC12 cells from LPS-induced damage by binding to Neurod1. In addition, SOX2OT knockdown relieved PC12 cell injury by inactivation of Janus kinase–signal transducer and activator of transcription pathway. SOX2OT promoted PC12 cell injury through modulating miR-331-3p/Neurod1 axis and activating Janus kinase–signal transducer and activator of transcription pathway. [ABSTRACT FROM AUTHOR]

Abstract Background Doxorubicin is the preferred chemotherapeuticdrug for osteosarcoma treatment of which clinical efficacy is limited because of its chemo-resistance and cardiac toxicity. It is necessary to develop the combination regimen with complementary molecular mechanisms to reduce the side effects and enhance sensitivity of Doxorubicin. EGCG is a polyphenol in green tea with antitumor bioactivity,which has been found that its combination with certain chemotherapeutic drugs could improve the antitumor efficiency. Methods In this study, MTT assay was used to detect the cell growth inhibition The CD133+/CD44+ cells were isolated from U2OS and SaoS2 cell lines using magnetic-activated cell sorting and identified by flow cytometry analysis. qRT-PCR was used for determining the relative mRNA levels of key genes. Immunofluorescence was performed to evaluate the autophagy flux alterations. Self-renewal ability was accessed by sphere-forming assay. Tumorigenicity in nude mice was preformed to evaluate tumorigenicity in vivo. Results We found that EGCG targeting LncRNA SOX2OT variant 7 produced synergistic effects with Doxorubicin on osteosarcoma cell growth inhibition. On the one hand, EGCG could reduce the Doxorubicin-induced pro-survival autophagy through decreasing SOX2OT variant 7 to improve the growth inhibition of Doxorubicin. On the other hand, EGCG could partially inactivate Notch3/DLL3 signaling cascade targeting SOX2OT variant 7 to reduce the stemness then abated drug-resistance of osteosarcoma cells. Conclusions This study will help to reveal the molecular mechanisms of synergistic effects of EGCG and Doxorubicin on OS chemotherapy and improve the clinical efficacy of chemotherapy as well as provide a basis for developing antitumor drugs targeting osteosarcoma stem cells.

Summary: SOX2 overlapping transcript (SOX2OT) is a long non-coding RNA associated with cancer pathogenesis. It contributes to a variety of cellular functions and recent evidence propounds its association with autophagy process. It has been showed that SOX2OT can regulate the expression of different autophagy associated factors in human cells with different mechanisms, however more remains to be investigated.

Long noncoding RNA SOX2OT is associated with myocardial fibrosis (MF) in heart failure (HF). This article aims to investigate the role of SOX2OT in MF. We constructed HF mouse models by subcutaneous injection of isoprenaline (ISO). Cardiac fibroblasts (CFs) were treated with ISO to induce MF.Hematoxylin‐eosin, Masson, and Sirius‐red staining were used to identify myocardial injury and collagen deposition in heart tissues. The relationship among SOX2OT, miR‐138‐5p, TGF‐β1, and Smad3 were evaluated by chromatin immunoprecipitation and luciferase reporter assay. The gene and protein expression were verified by quantitative real‐time PCR and western blot. We found that SOX2OT was up‐regulated in HF mice and ISO‐induced CFs. SOX2OT knockdown reduced myocardial injury and collagen deposition in HF mice. The expression of collagen I, α‐SMA, TGF‐β1, and p‐Smad3 were inhibited by SOX2OT down‐regulation in HF mice and ISO‐induced CFs. Furthermore, TGF‐β1 was a target gene of miR‐138‐5p and indirectly regulated by SOX2OT. SOX2OT promoted MF in HF by activating TGF‐β1/Smad3, and then Smad3 interacted with the SOX2OT promoter and formed a positive feedback loop. In conclusion, our work verifies that SOX2OT/Smad3 feedback loop promotes MF in HF. Thus, SOX2OT is potentially a novel therapeutic target for MF in HF. [ABSTRACT FROM AUTHOR]

Non-coding RNA elongated (lncRNAs) have recently attracted as molecules that regulate gene expression of the pluripotent properties (pluripotency) of stem cells. Recently our colleagues examined the role of one of these RNAs called SOX2OT in esophageal squamous cell carcinoma, and found a concomitant increase in its expression with some regulatory genes of cell proliferation. In the present study, using the design of suitable primers from SOX2OT gene, we investigated the effect of siRNA on expression of SOX2OT. [ABSTRACT FROM AUTHOR]

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Long non-coding RNA (lncRNA) SOX2 overlapping transcript (SOX2OT) has been shown to play an oncogenic role in diverse cancers, generating eight transcript variants. SOX2 is located in the third intron of SOX2OT. However, the biological function of SOX2OT in cervical cancer and implication with SOX2 remain to be further explored. In this study, we screened the expression pattern of different SOX2OT transcript variants in cervical cancer cells. Interestingly, both high-expression levels of SOX2OT transcript 7 (SOX2OT-7) and SOX2 were detected in C-33A (HPV−) and SiHa (HPV16+) cells. Thus, C-33A and SiHa cells were conducted to investigate the effects of SOX2OT on cell growth, migration and invasion. Finally, rescue experiments were performed to confirm the role of SOX2 in SOX2OT-mediated regulation of cervical cancer progression. The results showed that knockdown of SOX2OT suppressed cell viability, arrested cell cycle and ameliorated migration and invasion ability of C-33A and SiHa cells. Ectopic expression of SOX2OT-7 exacerbated cervical cancer cell proliferation, migration and invasion. In addition, we found that the expression levels and protein stability of SOX2 were positively regulated by SOX2OT. Inhibition of SOX2 could block the malignant phenotypes of C-33A and SiHa cells by SOX2OT-7. In conclusion, these findings indicate that lncRNA SOX2OT contributes to the growth, migration and invasion of cervical cancer cells by modulating SOX2. Importantly, we demonstrate that the transcript SOX2OT-7 may be a novel and promising biomarker for both HPV− and HPV16+ cervical cancer. [ABSTRACT FROM AUTHOR]

Long non‐coding RNA Sox2 overlapping transcript (SOX2OT) was reported to be involved in progression of multiple cancers. However, the role and mechanism of SOX2OT in multiple myeloma (MM) has yet to be unravelled. In the present study, elevated SOX2OT levels are reported in MM cell lines and patient samples as compared to normal plasma cells (nPCs) and healthy donors, respectively. Knock‐down of SOX2OT led to a significant inhibition of cell proliferation, arrested cells at G0/G1 phase and induced cell apoptosis in MM samples in vitro, as well as slowed the growth of tumours in vivo. Additionally, our data indicated that SOX2OT functioned as a competing endogenous RNA (ceRNA) in MM cells that regulated miR‐144‐3p expression. Repression of miR‐144‐3p reversed the inhibition of MM development due to SOX2OT knock‐down. Our data also revealed that SOX2OT regulated the expression of the cellular‐mesenchymal to epithelial transition factor (c‐MET, a known target of miR‐143‐3p) by functioning as a sponge of miR‐144‐3p in MM samples. These data support that SOX2OT promotes MM progression through regulating the miR‐144‐3p/c‐MET axis, suggesting that SOX2OT might be as a potential therapeutic target for MM. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence indicates that long non-coding RNAs (lncRNAs) are potential biomarkers and key regulators of tumour development and progression. SOX2 overlapping transcript (SOX2OT) is a novel lncRNA that acts as a potential biomarker and is involved in the development of cancer and cancer stem cells. However, the clinical significance and molecular mechanism of SOX2OT in bladder cancer are still unknown. Methods: The expression level of SOX2OT was determined by RT-qPCR in a total of 106 patients with urothelial bladder cancer and in different bladder cancer cell (BCC) lines. Bladder cancer stem cells (BCSCs) were isolated from BCCs using flow cytometry based on the stem cell markers CD44 and ALDH1. Loss-of-function experiments were performed to investigate the biological roles of SOX2OT in the stemness phenotype of BCSCs. Comprehensive transcriptional analysis, RNA FISH, dual-luciferase reporter assays and western blots were performed to explore the molecular mechanisms underlying the functions of SOX2OT. Results: SOX2OT was highly expressed in bladder cancer, and increased SOX2OT expression was positively correlated with a high histological grade, advanced TNM stage and poor prognosis. Further experiments demonstrated that knockdown of SOX2OT inhibited the stemness phenotype of BCSCs. Moreover, inhibition of SOX2OT delayed xenograft tumour growth and decreased metastases in vivo. Mechanistically, we found that SOX2OT was mainly distributed in the cytoplasm and positively regulated SOX2 expression by sponging miR-200c. Furthermore, SOX2 overexpression reversed the SOX2OT silencing-induced inhibition of the BCSC stemness phenotype. Conclusion: This study is the first to demonstrate that SOX2OT plays an important regulatory role in BCSCs and that SOX2OT may serve as a potential diagnostic biomarker and therapeutic target in bladder cancer. [ABSTRACT FROM AUTHOR]

Abstract Background Accumulating evidence has highlighted the potential role of long non-coding RNAs (lncRNAs) in the biological behaviors of glioblastoma stem cells (GSCs). Here, we elucidated the function and possible molecular mechanisms of the effect of lncRNA-SOX2OT on the biological behaviors of GSCs. Results Real-time PCR demonstrated that SOX2OT expression was up-regulated in glioma tissues and GSCs. Knockdown of SOX2OT inhibited the proliferation, migration and invasion of GSCs, and promoted GSCs apoptosis. MiR-194-5p and miR-122 were down-regulated in human glioma tissues and GSCs, and miR-194-5p and miR-122 respectively exerted tumor-suppressive functions by inhibiting the proliferation, migration and invasion of GSCs, while promoting GSCs apoptosis. Knockdown of SOX2OT significantly increased the expression of miR-194-5p and miR-122 in GSCs. Dual-luciferase reporter assay revealed that SOX2OT bound to both miR-194-5p and miR-122. SOX3 and TDGF-1 were up-regulated in human glioma tissues and GSCs. Knockdown of SOX3 inhibited the proliferation, migration and invasion of GSCs, promoted GSCs apoptosis, and decreased TDGF-1 mRNA and protein expression through direct binding to the TDGF-1 promoter. Over-expression of miR-194-5p and miR-122 decreased the mRNA and protein expression of SOX3 by targeting its 3’UTR. Knockdown of TDGF-1 inhibited the proliferation, migration and invasion of GSCs, promoted GSCs apoptosis, and inhibited the JAK/STAT signaling pathway. Furthermore, SOX3 knockdown also inhibited the SOX2OT expression through direct binding to the SOX2OT promoter and formed a positive feedback loop. Conclusion This study is the first to demonstrate that the SOX2OT-miR-194-5p/miR-122-SOX3-TDGF-1 pathway forms a positive feedback loop and regulates the biological behaviors of GSCs, and these findings might provide a novel strategy for glioma treatment.

Endoplasmic reticulum (ENR) stress perturbs cell homeostasis and induces the unfolded protein response (UPR). In breast cancer, this process is activated by oestrogen deprivation and is associated with tamoxifen resistance. We present evidence that the transcription factor SOX2 and the long noncoding RNA SOX2 overlapping transcript (SOX2OT) are upregulated in oestrogen receptor-positive (ER+) breast cancer and in response to oestrogen deprivation. We examined the effect of the UPR on SOX2 and SOX2OT expression and the effect of SOX2OT on UPR pathways in breast cancer cell lines. The induction of the UPR by thapsigargin or glucose deprivation upregulates SOX2OT expression. This upregulation is also shown with the anti-oestrogen 4OH-tamoxifen and mTOR inhibitor everolimus in ER + breast cancer cells that are sensitive to oestrogen deprivation or everolimus treatment. SOX2OT overexpression decreased BiP and PERK expression. This effect of SOX2OT overexpression was confirmed on BiP and PERK pathway by q-PCR. Our results show that a long noncoding RNA regulates the UPR and evince a new function of SOX2OT as a participant of ENR stress reprogramming of breast cancer cells.

Researches establish an indispensable role of mitochondrial dysfunction in septic cardiomyopathy. We aimed to investigate the effects of long noncoding RNA (LncRNA) SOX2 overlapping transcript (SOX2OT) on mitochondrial dysfunction in septic cardiomyopathy. We observed an obvious overexpression of SOX2OT in septic hearts and cardiomyocytes. Knockdown of SOX2OT in mice recovered the reduced cardiac function, and improved the mitochondrial membrane potential impaired by lipopolysaccharide (LPS). SOX2OT overexpressed mice showed the opposite situation. In parallel, knockdown of SOX2OT in cardiomyocytes restored the mitochondrial membrane potential, along with reduced mitochondrial reactive oxygen species production induced by LPS, while overexpression of SOX2OT reversed these effects. Mechanistically, SOX2OT could regulate mitochondrial dysfunction in septic cardiomyopathy via SOX2. In general, SOX2OT contributed to mitochondrial dysfunction progression via inhibiting SOX2 expression in septic cardiomyopathy, which may provide a new insight for treatment of septic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Early diagnosis of non‐small cell lung cancer (NSCLC) is essential for patient treatment and prognosis. Long noncoding RNA (lncRNA) have potential roles in tumor initiation and differentiation. The objective of this study was to investigate whether the circulating lncRNA, growth arrest‐specific transcript 5 (GAS5) and SOX2 overlapping transcript (SOX2OT), could be used as noninvasive biomarkers for NSCLC diagnosis. Moreover, we aimed at evaluating the association between lncRNA and the clinicopathological features of NSCLC in order to predict the cancer prognosis. The results showed significant downregulation of GAS5 expression and upregulation of SOX2OT in NSCLC patients compared with controls (P < 0.001). Furthermore, the expression level of GAS5 was declined in stage IV of NSCLC, but SOX2OT expression was increased sharply in stages III and IV. The expression levels of lncRNAs were used to distinguish NSCLC patients from control with an area under curve of 0.81 (sensitivity 82.5% and specificity 80%) for GAS5 and 0.73 (sensitivity 76.3% and specificity 78.6%) for SOX2OT. The combination of GAS5 and SOX2OT showed differentiation NSCLC patients from controls with increased sensitivity (83.8) and specificity (81.4). In conclusion, the newly developed diagnostic panel involving of circulating GAS5 and SOX2OT could be perfect biomarker for diagnosis and prognosis of NSCLC. [ABSTRACT FROM AUTHOR]

Recent studies reported that long noncoding RNAs (LncRNAs) were involved in tumorigenesis of various human cancer types, including gastric cancer (GC) through targeting microRNAs (miRNAs/miRs). The present study investigated the biological functions of LncRNA SOX2 overlapping transcript (SOX2OT)/miR-194-5p axis and its underlying mechanism in the tumor progression of GC. The results showed that relative expression of LncRNA SOX2OT was highly upregulated while the expression of miR-194-5p was down-regulated in GC tissues and cell lines (MGC-803, SGC-7901, MKN-74). Knockdown of SOX2OT inhibited cell proliferation, invasion and migration of GC cells (MGC803, MKN-74) through reducing epithelial-mesenchymal transition (EMT). Moreover, miR-194-5p was predicted to be one of the targets of SOX2OT through bioinformatics analysis and was verified by luciferase reporter assay. miR-194-5p expression was negatively regulated by SOX2OT expression in GC cells and miR-194-5p inhibitor was found to counteract the inhibitory effects of SOX2OT short hairpin (sh)RNA on cell proliferation and mobility through enhancing EMT in GC cells. Taken together, the in vitro experiments revealed that knockdown of SOX2OT inhibited cell proliferation and mobility through suppressing EMT via targeting miR-194-5p in GC. In addition, results from in vivo experiments showed that knockdown of SOX2OT suppressed GC tumor growth and matrix metalloproteinase (MMP)-2 and MMP-9 expression through inhibiting EMT. Besides that, relative expression of miR-194-5p was increased in sh-SOX2OT group compared with sh-NC group. In summary, our study elucidated that the SOX2OT/miR-194-5p axis participated in the tumor progression of GC through regulation of EMT both in vitro and in vivo. Hence, targeting the SOX2OT/miR-194-5p axis may aid in establishing novel strategies for therapy of GC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Gastric cancer (GC) is the third leading cause of cancer-related death in the world. Dysfunction of long noncoding RNAs (lncRNAs) in cancers, especially those with role in pluripotency, are approved by increasing evidence. OBJECTIVE: SOX2 overlapping transcript (SOX2OT) lncRNA, is aberrantly expressed in different cancers; however its role in gastric cancer is still controversial. MATERIALS AND METHODS: In this study, the expression of SOX2OT was evaluated in 33 matched pair tumor and non-tumor gastric samples and AGS and MKN45 gastric and NTERA2 embryonic carcinoma cell lines by real time PCR. RESULTS: Our finding revealed a significant decrease in the expression of SOX2OT in gastric tumor samples compared to their matched non-tumor samples (P = 0.05) and also a lower expression in high grade compared to low grade of gastric malignancy. As we expected SOX2OT expression showed higher expression in NT2 compared to AGS and MKN45 cell lines. CONCLUSION: Simultaneous expression of SOX2 and SOX2OT was reported in some cancers. Regarding to the decreased expression of SOX2OT in the present study in concurrent with downregulation of SOX2 in our previous study, it seems that SOX2OT plays a tumor suppressor role in GC and may be useful biomarker for diagnosis of GC. [ABSTRACT FROM AUTHOR]

Background: Long noncoding RNA (lncRNA) Sox2 overlapping transcript (SOX2OT) has been reported to be upregulated in various types of cancers, including non-small-cell lung cancer (NSCLC). However, the biological role and underlying mechanism of SOX2OT activity in NSCLC remain largely unknown. This study aims to investigate the function and possible molecular mechanisms of SOX2OT in NSCLC. Materials and methods: Quantitative real-time polymerase chain reaction was used to detect SOX2OT expression, and cellular proliferation, migration, and invasion were measured using cell counting kit-8, wound healing, and Transwell invasion assays, respectively. Western blotting was used to determine protein expression. Starbase 2.0 and luciferase reporter assay were utilized to identify the molecular target of SOX2OT. Results: Here, we discovered that SOX2OT was markedly upregulated in NSCLC tissues and cell lines. Knockdown of SOX2OT inhibited the proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) process in NSCLC cells. Moreover, we explored the regulatory mechanism of SOX2OT and found that SOX2OT directly bound microRNA 132 (miR-132) in NSCLC cells. Importantly, miR-132 inhibition partially reversed the SOX2OT knockdown-mediated inhibitory effect on cell proliferation, migration, invasion, and EMT process. We also found that SOX2OT could regulate zinc finger E-box-binding homeobox 2 (a target of miR-132) expression, which played crucial roles in tumor cell proliferation and invasion. Conclusion: These findings indicated that SOX2OT was a noncoding oncogene that exerted important regulatory functions in NSCLC via sponging miR-132 and might represent a novel strategy for overcoming this disease. [ABSTRACT FROM AUTHOR]

SOX2 overlapping transcript (Sox2ot), a long noncoding RNA (lncRNA), was initially found a close concomitant expression pattern of SOX2 gene . Multiple studies have demonstrated that the relatively upregulated Sox2ot could be observed in different types of cancer tissues and effectively promotes cell proliferation, invasion, and tumorigenesis in vitro. In the present study, we aimed to detect the crucial prognostic role of Sox2ot in cholangiocarcinoma (CCA) patients' clinicopathologic features and evaluated the correlation between Sox2ot expression and CCA patients overall survival. 58 CCA patients who underwent surgical treatment were recruited for the investigation. Sox2ot expression levels estimated by the quantitative real-time PCR (qRT-PCR) showed that both clinical tissues and cell lines possessed the overexpressed states and the upregulation of Sox2ot significantly associated with lymph node invasion ( p = 0.0308), TNM stage ( p = 0.0072) and postoperative recurrence ( p = 0.0019). The Kaplan-Meier curve showed a strong association between Sox2ot and overall survival (OS) and multivariate analysis confirmed this finding. Furthermore, the proliferation, migration and invasion assays were carried out with RBE and QBC939 cell lines and the knockdown of Sox2ot in all experiments could remarkably decrease malignant biological behaviors. Taken together, lncRNA Sox2ot indicates an unfavorable prognostic biomarker and potential therapeutics target for CCA patients. [ABSTRACT FROM AUTHOR]

The transcription regulator Yin Yang-1 (YY1) serves as a tumor suppressor in pancreatic ductal adenocarcinoma (PDAC). However, the function of YY1 in proliferation of PDAC cells remains to be clarified. In this study, we found that overexpression of YY1 suppressed proliferation and decreased the expression of long non-coding RNA (lncRNA) SOX2OT and its potential target gene SOX2 in PDAC cells. Luciferase reporter, electrophoretic mobility shift (EMSA), and chromatin immunoprecipitation (ChIP) assays revealed binding of YY1 to the SOX2OT promoter. Moreover, YY1 suppressed PDAC cell proliferation through SOX2OT transcriptional inhibition and subsequent decreased SOX2 expression. In addition, YY1 expression was statistically negatively correlated with SOX2OT and SOX2 expression in PDAC tissues and lower level expression of SOX2OT predicted better outcome in PDAC patients. These results confirmed the anti-proliferation effect of YY1 on PDAC cells, which was associated with SOX2 down-regulation in a SOX2OT-dependent mechanism. Although other undiscovered mechanisms may be involved in the YY1-mediated tumor suppression role, the present study suggests that SOX2OT may act as a tumor promotor in PDAC and may represent a valuable diagnostic and therapeutic target. [ABSTRACT FROM AUTHOR]

SOX2 overlapping transcript (SOX2OT) is a long non-coding RNA (lncRNA) which harbors one of the major regulators of pluripotency, SOX2 gene, in its intronic region. SOX2OT gene is mapped to human chromosome 3q26.3 (Chr3q26.3) locus and is extended in a high conserved region of over 700 kb. Little is known about the exact role of SOX2OT; however, recent studies have demonstrated a positive role for it in transcription regulation of SOX2 gene. Similar to SOX2, SOX2OT is highly expressed in embryonic stem cells and down-regulated upon the induction of differentiation. SOX2OT is dynamically regulated during the embryogenesis of vertebrates, and delimited to the brain in adult mice and human. Recently, the disregulation of SOX2OT expression and its concomitant expression with SOX2 have become highlighted in some somatic cancers including esophageal squamous cell carcinoma, lung squamous cell carcinoma, and breast cancer. Interestingly, SOX2OT is differentially spliced into multiple mRNA-like transcripts in stem and cancer cells. In this review, we are describing the structural and functional features of SOX2OT, with an emphasis on its expression signature, its splicing patterns and its critical function in the regulation of SOX2 expression during development and tumorigenesis.

Breast cancer is a molecularly heterogeneous disease which necessitates a search for markers to provide a more specific classification of this disorder. Long noncoding RNAs as the important subset of noncoding transcripts have been shown to be involved in tumorigenic processes. So, they may be used as markers for early detection of cancer and evaluation of cancer prognosis. In addition, they can be applied as therapeutic targets. In this study, we analyzed expression of four long noncoding RNAs (lncRNAs) namely SOX2OT, PTPRG-AS1, ANRASSF1, and ANRIL in 38 breast cancer tissues and their adjacent noncancerous tissues (ANCTs). ANRASSF1 expression was not detected in any noncancerous tissue. All lncRNAs showed significant overexpression in tumor tissues compared with ANCTs. No association was found between gene expressions and individual clinical data such as tumor stage, grade, size and hormone receptor status except for ANRASSF1 expression and Her2/neu status. In addition, ANRASSF1 and ANRIL expressions were significantly higher in triple negative samples. This study suggests a putative role for these lncRNAs in breast cancer and implies that they can be used as potential cancer biomarkers. [ABSTRACT FROM AUTHOR]

SOX2 overlapping transcript (SOX2OT) is a long non-coding RNA which harbors one of the major regulators of pluripotency, SOX2 gene, in its intronic region. SOX2OT gene is mapped to human chromosome 3q26.3 (Chr3q26.3) locus and is extended in a high conserved region of over 700 kb. Little is known about the exact role of SOX2OT; however, recent studies have demonstrated a positive role for it in transcription regulation of SOX2 gene. Similar to SOX2, SOX2OT is highly expressed in embryonic stem cells and down-regulated upon the induction of differentiation. SOX2OT is dynamically regulated during the embryogenesis of vertebrates, and delimited to the brain in adult mice and human. Recently, the disregulation of SOX2OT expression and its concomitant expression with SOX2 have become highlighted in some somatic cancers including esophageal squamous cell carcinoma, lung squamous cell carcinoma, and breast cancer. Interestingly, SOX2OT is differentially spliced into multiple mRNA-like transcripts in stem and cancer cells. In this review, we are describing the structural and functional features of SOX2OT, with an emphasis on its expression signature, its splicing patterns and its critical function in the regulation of SOX2 expression during development and tumorigenesis. [ABSTRACT FROM AUTHOR]

Sox2 overlapping transcript (Sox2ot) is a long noncoding RNA (lncRNA), localized on human chromosome 3q26.33, which is frequently amplified in lung squamous cell carcinomas (SCCs). However, its roles in lung cancer remain under investigation. In this study, we found that Sox2ot was up-regulated over two folds in 53.01% of human primary lung cancers (44/83). The expression level of Sox2ot is significantly higher in SCCs than that in adenocarcinomas (ADCs) of the lung. Further study found high Sox2ot expression predicted poor survival in lung cancer patients (P=0.0053), implying Sox2ot is a novel prognostic factor. In two human lung cancer cell lines, HCC827 and SK-MES-1, knocking down Sox2ot inhibited cell proliferation by inducing G2/M arrest, with a concomitant decrease of cells in S phase. Reduced protein levels of Cyclin B1 and Cdc2 were also observed. Importantly, knocking down Sox2ot decreased EZH2 expression and reintroduction of EZH2 allowed Sox2ot knockdown cells progressed through G2/M phase, which correlates with the restoration of Cyclin B1 and Cdc2 expressions. Altogether, our data suggested that Sox2ot plays an important role in regulating lung cancer cell proliferation, and may represent a novel prognostic indicator for the disease. [ABSTRACT FROM AUTHOR]