Two Novel Splice Variants of SOX2OT, SOX2OT-S1, and SOX2OT-S2 are Coupregulated with SOX2 and OCT4 in Esophageal Squamous Cell Carcinoma

Shahryari, Ali; Rafiee, Mahmoud Reza; Fouani, Youssef; Oliae, Nasrin Alipour; Samaei, Nader Mansour; Shafiee, Mohammad; Semnani, Shahryar; Vasei, Mohammad; Mowla, Seyed Javad

doi:10.1002/stem.1542

Cited by 113 publications

(115 citation statements)

References 43 publications

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“…Hou et al (16) reported that knockdown of SOX2OT inhibited the proliferation of lung cancer cells by inducing G2/M arrest. Another report by Shahryari et al (17) suggested that knockdown of SOX2OT caused preferable cell distribution in G1 and sub-G1 phases in esophageal squamous cell carcinoma, which was consistent with our results. These findings suggest that SOX2OT may inhibit cell proliferation by arresting cell cycle progression in certain tumor types.…”

Section: Discussionsupporting

confidence: 94%

“…The gene does not contain open reading frames, however, it is spliced into several transcripts that are microRNA-like (14). The concurrent expression pattern between lncRNA, SOX2OT and SOX2 in certain types of human cancer and human stem cells indicates the possibility that they may be involved in specific similar signaling pathways and engage in co-regulation, which has been validated by some recent studies (15)(16)(17). SOX2OT was postulated to participate in SOX2 transcription, acting as an important enhancer (14).…”

Section: Introductionmentioning

confidence: 83%

“…Interrupted cell cycle progression was also evidenced by the dysregulation of key cell cycle regulators, cyclin B1 and Cdc25C. Cyclin B1 is a regulatory protein involved in the process of mitosis (17). Cdc25C protein participates to control the entry of cells into different phases during cell cycle progression in mitosis (24).…”

Section: Discussionmentioning

confidence: 99%

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Long non-coding RNA SOX2OT promotes cell proliferation and motility in human ovarian cancer

Han

Zhang

et al. 2017

Exp Ther Med

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Abstract. Ovarian cancer is one of the most common malignant gynecological cancers. Although conventional chemotherapies have improved the treatment of patients with ovarian cancer, the mortality rate remains high. Hence, it is crucial that the detailed mechanisms that promote ovarian cancer are urgently identified. Therefore, reverse transcription-quantitative polymerase chain reaction was used to reveal the relative transcript levels. Colony formation assay and cell cycle assay were performed in siRNA-treated cells. Transwell assay and western blot assays were also conducted. The results showed that the expression of long non-coding RNA SRY-box 2 overlapping transcript (SOX2OT) was upregulated in clinical ovarian cancer tissues and in cultured ovarian cancer cells (HO-8910 and HO-8910PM). High expression of SOX2OT negatively correlated with the prognosis of patients with ovarian cancer. Knockdown of SOX2OT by specific small interfering RNA against SOX2OT suppressed the colony formation capacity of invasive ovarian cancer cells and resulted in cell cycle arrest in G0/G1 phase. Key cell cycle regulators, cyclin B1 and cell division cycle 25C, were consistently downregulated by the knockdown of SOX2OT. Furthermore, knockdown of SOX2O Tinhibited cell migration, cell invasion and decreased the expression of mesenchymal protein N-cadherin, whereas the expression of epithelial protein E-cadherin was increased in ovarian cancer cells. Overall, SOX2OT expression levels correlated with the prognosis of patients with ovarian cancer, and SOX2OT promoted cell proliferation and motility in ovarian cancer cells. These findings indicated that SOX2OT may serve as a potential therapeutic target in the treatment of ovarian cancer.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 83%

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Long non-coding RNA SOX2OT promotes cell proliferation and motility in human ovarian cancer

Han

Zhang

et al. 2017

Exp Ther Med

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“…This composite may drive pluripotency via SOX2‐OCT4 and switch on lineage‐related genes through Oct4's recruitment of Tcf/Lef factors 23. As a high level of OCT4 expression was detected in the Eca109 cell line,28 we inhibited the expression of OCT4 via the lentiviral infection system with plasmid vectors encoding OCT4‐shRNA. The results indicated that OCT4 positively regulated LEF1 expression.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of association of OCT4 with LEF1 expression in esophageal squamous cell carcinoma and their impact on epithelial‐mesenchymal transition, invasion, and migration

Zhao

Huang

et al. 2018

Cancer Medicine

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Esophageal squamous cell carcinoma (ESCC) is a malignant disease with poor prognosis. Because of early metastasis prior to diagnosis and therapeutic resistance, ESCC has become one of the leading causes of cancer‐related death. Here, we investigated the clinicopathological significance of the association of octamer‐binding transcription factor 4 (OCT4) with lymphoid enhancer‐binding factor 1 (LEF1) expression and the potential molecular mechanism in the epithelial‐mesenchymal transition (EMT), invasion, and migration of ESCC. The expression of OCT4 and LEF1 was detected via immunohistochemistry analysis. High levels of LEF1 expression were observed in 95 ESCC specimens and were obviously associated with aberrant clinicopathological features and poor patient prognosis. Our previous study showed that OCT4 expression level is elevated in ESCC, and statistical analysis showed that the elevated expression of OCT4 and LEF1 in ESCC was significantly associated with histologic grade, lymph node metastasis, TNM stage, and poor patient prognosis. The specific inhibition of OCT4 expression via a lentivirus encoding OCT4‐shRNA (LV‐shOCT4) in Eca109 cells led to decreased levels of OCT4 and LEF1 in vitro. Additionally, we applied a rescue strategy by infecting LV‐shOCT4 Eca109 cells with a LEF1 overexpression plasmid (p‐LEF1) and detected changes in EMT, migration, and invasion. Unsurprisingly, the p‐LEF1 group exhibited greater EMT, invasion, and migration than did the LV‐shOCT4 and negative control groups. This study demonstrates for the first time the relationship between OCT4 and LEF1 expression. The combination of high expression of OCT4 and LEF1 was associated with clinicopathological features of atypical patients, and this combination might be an ideal prognostic factor in ESCC. OCT4 positively regulated LEF1 expression, and LEF1 mediated the effects of OCT4 in cancer cell EMT, invasion, and migration. The data presented here suggest that the inhibition of OCT4‐LEF1 signaling may be a new therapeutic target for the treatment of ESCC.

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“…SOX2OT'nin açık okuma çerçevesi (ORF) olmadığı ancak birkaç mRNA benzeri transkripte dönüştüğü bilinmektedir. SOX2OT ve Sox2'nin kök hücre ve bazı kanserlerde benzer ifadelenme paternlerinin olduğu, hatta SOX2OT'nin Sox2 transkripsiyonunu düzenlediği ileri sürülmüştür (9).…”

Section: Sox2 Geni Ve Proteiniunclassified

Kanserde yeni bir hedef haline gelen çok yönlü Sox2 geni

Turaçlı¹,

Ekmekçi²

2016

Ege Tıp Dergisi

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ÖzSox2 proteini, farklılaşmamış erken embriyo kök hücrelerinin ve çeşitli yetişkin kök hücrelerinin gelişimi ve devamlılığının düzenlenmesinde rol oynayan bir transkripsiyon faktörüdür. Sox2, diğer pluripotensi faktörleri gibi posttranskripsiyonel ve post-translasyonel değişimlere uğramakta, böylece DNA'ya bağlanma aktivitesi değişebilmektedir. Sox2, kanser hücrelerinin çoğalması, invazyon, göç ve metastazında, tümör hücre ve kök hücre statüsünün devamında, hücresel programlama, apoptoz ve kemodirenç gelişimi gibi pek çok kanser aşamasında yer almaktadır. Bazı farklı bulgulara karşın çoğunlukla Sox2'nin kanser hücrelerinde anti-apoptotik bir faktör olarak çalıştığı konusunda uzlaşma vardır. Bu derlemede, Sox2'nin kök hücre devamlılığı, farklılaşması ve sinyal iletimindeki rollerini, bunun yanında gen çoğalmasıyla onkojenik özelliği kazanmasını ve moleküler hedef olarak kullanılma potansiyelini de kapsayan çok yönlü özelliklerini kısaca tartışacağız.Anahtar Sözcükler: Sox2, kanser. Abstract Sox2 protein is a transcription factor which is important for the maintenance and regulation of the permanence of undifferentiated embryonic and adult stem cells. Like the other pluripotency factors, Sox2 can be regulated by posttranscriptional and post-translational modifications which affect its binding ability to DNA. Sox2 involves in many cellular events in the initiation and progression of tumorigenesis such as proliferation of cancer cells, invasion

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Two Novel Splice Variants of SOX2OT, SOX2OT-S1, and SOX2OT-S2 are Coupregulated with SOX2 and OCT4 in Esophageal Squamous Cell Carcinoma

Cited by 113 publications

References 43 publications

Long non-coding RNA SOX2OT promotes cell proliferation and motility in human ovarian cancer

Long non-coding RNA SOX2OT promotes cell proliferation and motility in human ovarian cancer

Prognostic value of association of OCT4 with LEF1 expression in esophageal squamous cell carcinoma and their impact on epithelial‐mesenchymal transition, invasion, and migration

Kanserde yeni bir hedef haline gelen çok yönlü Sox2 geni

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