LncRNA UCA1/miR-124 axis modulates TGFß1-induced epithelial-mesenchymal transition and invasion of tongue cancer cells through JAG1/Notch signaling.

Tongue cancer remains a massive threat to public health due to the high rate of metastasis. Tumor cell epithelial-mesenchymal transition (EMT), which can be induced by transforming growth factor ß1 (TGFß1), has been regarded as a significant contributor to cancer invasion and migration. In our previous study, long noncoding RNA (lncRNA) MALAT1/miR-124/JAG1 axis modulates the growth of tongue cancer. In addition to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), another lncRNA, urothelial cancer associated 1 (UCA1), can promote EMT and cancer metastasis. In the present study, UCA1 was overexpressed in tongue cancer tissues and cell lines. UCA1 overexpression was correlated to the poorer prognosis of patients with tongue cancer. UCA1 knockdown significantly suppressed TGFß1-induced tongue cancer cell invasion and EMT by decreasing vimentin and increasing E-cadherin. Regarding the molecular mechanism, UCA1 could directly bind to microRNA-124 (miR-124) and negatively regulate each other. UCA1 knockdown ameliorated, whereas miR-124 inhibition exacerbated TGFß1-induced EMT and invasion in tongue cancer cells through miR-124 downstream jagged 1 (JAG1) and Notch signaling. Moreover, miR-124 inhibition partially impaired the effect of UCA1 knockdown. In tongue cancer tissues, miR-124 expression was remarkably decreased, whereas JAG1 mRNA expression was increased. miR-124 was negatively correlated with UCA1 and JAG1. UCA1 and JAG1 were positively correlated. In summary, we provided a novel mechanism by which the EMT process and cancer cell invasion in tongue cancer could be modulated from the perspective of lncRNA-miRNA-mRNA regulation.

TGFß1-Smad3-Jagged1-Notch1-Slug signaling pathway takes part in tumorigenesis and progress of tongue squamous cell carcinoma.

BACKGROUND: TGFß1 and Smad3 play an important role in the process of EMT. TGFß1 regulates the expression of Jagged1 by modulating Notch signaling. Jagged1 is related to tumor invasion, metastasis, chemotherapy resistance, and tumor immune escape. The aims of this study are to examine deregulation of TGFß1-Smad3-Jagged1-Notch1-Slug signaling in TSCC and to investigate its roles in TSCC progression. MATERIALS AND METHODS: Notch1, Smad3, Jagged1 and Slug proteins and mRNA expression were detected in specimens from 89 cases of patients. We analyzed the correlation between their expressions and histological grade, clinical stage and lymph node metastasis. RESULTS: Notch1, Smad3, Jagged1 and Slug mRNA expressions in TSCC were higher than normal tissue (P <0.05). The protein expression of Notch1 and Smad3 in TSCC were higher (χ(2) =7.30, P <0.01 and χ(2) = 5.84, P <0.05). Notch1 and Smad3 expressions were correlated with clinical stage (χ(2) =18.81, P<0.01; χ(2) =22.29, P<0.01), but not Jagged1 (χ(2) =0.53, P>0.05). The Slug protein expression was correlated with clinical stage. The positive rate of Notch1 was higher in lymph node metastases positive cases (χ(2) =7.30, P<0.01). Moreover, higher expression of Jagged1 was found in lymph node positive cases (χ(2) =10.82, P<0.01). CONCLUSIONS: The key protein expression in TGFß1-Smad3-Jagged1-Notch1-Slug signaling pathway significantly correlated with the clinicopathological features of TSCC patients. It's potential as a biomarker and a novel therapeutic target for TSCC patients at risk of metastasis. It may play an irreplaceable role in TSCC progression which may attribute to promoting EMT which enhances cell migration, invasion and metastasis.

A novel mechanism of the lncRNA PTTG3P/miR-142-5p/JAG1 axis modulating tongue cancer cell phenotypes through the Notch1 signaling.

Tongue cancer is the most prevalent type of oral cancer. Our previous study revealed that JAG1 exerted an oncogenic effect on tongue carcinoma through the JAG1/Notch pathway. In this study, a lncRNA PTTG3P which was upregulated in tongue cancer, was found to be positively correlated with JAG1. In CAL-27 and SCC4 cells, PTTG3P silencing significantly decreased JAG1 proteins and the ability of tongue tumor cells to proliferate and migrate. PTTG3P overexpression exhibited the opposite effect on CAL-27 and SCC4 cells. PPTG3P directly bound miR-142-5p, and miR-142-5p directly bound 3'UTR of JAG1 and inhibited the expression levels of JAG1. As opposed to PTTG3P silencing, miR-142-5p inhibition increased JAG1 protein levels and tongue cancer cell proliferation and migration; moreover, miR-142-5p inhibition substantially reversed the effects of PTTG3P silencing. Finally, the PPTG3P/miR-142-5p axis regulated the level of NICD, Notch downstream c-myc, and cyclin D1, as well as EMT markers Snail, Twist, and Vimentin. In conclusion, the PTTG3P/miR-142-5p axis modulates tongue cancer aggressiveness through JAG1, potentially through a JAG1/Notch signaling pathway.

[Retracted] Long non­coding RNA MALAT1 interacts with miR­124 and modulates tongue cancer growth by targeting JAG1.

We wish to retract our research article entitled "Long non­coding RNA MALAT1 interacts with miR­124 and modulates tongue cancer growth by targeting JAG1" published in Oncology Reports 37 2087­2094, 2017. Following the publication of this article, it was drawn to our attention that this paper bore numerous similarites with an article published previously in the journal OncoTargets and Therapy. Although all the data reported in our study were original, we recognize that it was not appropriate that we should have modelled our paper on previously published articles as a template on which to base the writing of our paper. Therefore, we have agreed to follow the Editor's recommendation that this paper be retracted from the publication. All the named authors agree to this retraction. We sincerely apologize to the Editor and the readership of the Journal for our action, and regret any inconvenience this has caused. [the original article was published in the Oncology Reports 37: 2087­2094, 2017; DOI: 10.3892/or.2017.5445].

Long non-coding RNA MALAT1 interacts with miR-124 and modulates tongue cancer growth by targeting JAG1.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNA (lncRNA), was the earliest discovered to be correlated with cancer and contributes to the initiation and development of several types of tumors. Dysregulation of MALAT1 expression is frequently observed in many types of cancer such as gastric cancer, esophageal squamous cell carcinoma and glioma. To date, the role of MALAT1 and the underlying mechanisms in tongue cancer development remain unclear. In the present study, we studied the influence of MALAT1 on tongue cancer cell lines and clinical tongue cancer samples so as to detect its function and the underlying mechanism. In the present study, lncRNA-MALAT1 was specifically upregulated in tongue cancer cell lines and overexpression promoted tongue cancer cell growth by targeting miR-124. Knockdown of MALAT1 suppressed the growth and invasion of human tongue cancer cells and inhibited metastasis in vitro and in vivo. In addition, miR-124-dependent jagged1 (JAG1) regulation was required for MALAT1-induced tongue cancer cell growth. Our data revealed that MALAT1 inhibited tongue cancer cell growth and metastasis through miR-124-dependent JAG1 regulation. In conclusion, we revealed that MALAT1 may play an oncogenic role by increasing proliferation and metastasis of tongue cancer and is a potential therapeutic target in human tongue cancer.