miR-222 targets VGLL4 to promote growth of tongue squamous cell carcinoma

2020 ◽  
Vol 10 (1) ◽  
pp. 102-111
Author(s):  
Liang Shi ◽  
Xiaobin Song ◽  
Ketao Wang ◽  
Shaohua Liu ◽  
Yong Wang

We investigated whether regulation of VGLL4 by miR-222 affects proliferation, migration, invasion, and apoptosis in human tongue squamous cell carcinoma (TSCC) cells. Nanometer Magnetic beads were prepared to extract RNA in CAL27/human oral keratinocytes (HOK). Correlation between expression of miR-222 and VGLL4 in CAL27/human oral keratinocytes (HOK) was analyzed using RT-PCR and western blot. The cellular effects of miR-222/VGLL4 interactions were detected by cck8, transwell, and cell scratch assays, and flow cytometry after miR-222 was silenced or overexpressed in CAL27 cells. We assessed tumor growth in vivo, in a subcutaneous tumor model in mice, and assessed VGLL4 protein expression in tumors by immunohistochemistry. We found that miR-222 expression is higher in CAL27 cells than that in HOK cells. VGLL4 was highly expressed in HOK cells relative to CAL27 cells. When miR-222 was overexpressed, VGLL4 mRNA expression was reduced in CAL27 cells, and protein expression was reduced in the in vivo tumor model. Thus, miR-222 may down-regulate VGLL4 to promote proliferation, migration, and invasion of TSCC cells.

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ying Zheng ◽  
Bowen Zheng ◽  
Xue Meng ◽  
Yuwen Yan ◽  
Jia He ◽  
...  

Abstract Background Tongue squamous cell carcinoma (TSCC) is a most invasive cancer with high mortality and poor prognosis. It is reported that lncRNA DANCR has implications in multiple types of cancers. However, its biological role and underlying mechanism in TSCC progress are not well elucidated. Methods Our present study first investigated the function of DANCR on the proliferation, migration and invasion of TSCC cells by silencing or overexpressing DANCR. Further, the miR-135a-5p-Kruppel-like Factor 8 (KLF8) axis was focused on to explore the regulatory mechanism of DANCR on TSCC cell malignant phenotypes. Xenografted tumor growth using nude mice was performed to examine the role of DANCR in vivo. Results DANCR knockdown reduced the viability and inhibited the migration and invasion of TSCC cells in vitro, while ectopic expression of DANCR induced opposite effects. In vivo, the tumor growth and the expression of matrix metalloproteinase (MMP)-2/9 and KLF8 were also blocked by DANCR inhibition. In addition, we found that miR-135-5p directly targeted DANCR, which was negatively correlated with DANCR on TSCC progression. Its inhibition reversed the beneficial effects of DANCR silence on TSCC malignancies. Furthermore, the expression of KLF8 evidently altered by both DANCR and miR-135a-5p. Silencing KLF8 using its specific siRNA showed that KLF8 was responsible for the induction of miR-135a-5p inhibitor on TSCC cell malignancies and MMP-2/9 expression. Conclusions These findings, for the first time, suggest that DANCR plays an oncogenic role in TSCC progression via targeting miR-135a-5p/KLF8 axis, which provides a promising biomarker and treatment approach for preventing TSCC.


2020 ◽  
Vol 2020 ◽  
pp. 1-21 ◽  
Author(s):  
Danfeng Xue ◽  
Shu-Ting Pan ◽  
Xiongming Zhou ◽  
Fangfei Ye ◽  
Qun Zhou ◽  
...  

Cisplatin is widely used in the treatment of tongue squamous cell carcinoma (TSCC), but its clinical efficacy is limited by drug resistance and toxic side effects. Hence, a novel compound capable of enhancing the anticancer effect of cisplatin while reducing the side effects is urgently needed. We have previously shown that plumbagin (PLB), an anticancer phytochemical, is able to inhibit the growth of TSCC in vitro and in vivo. The objective of this study was to investigate the effect of PLB in reversing the resistance of TSCC to cisplatin as well as its molecular mechanisms. Here, we found that PLB enhances cisplatin-induced cytotoxicity, apoptosis, and autophagy in CAL27 and cisplatin-resistant CAL27/CDDP cells. PLB could inhibit the viability and growth of TSCC cells by increasing the production of intracellular reactive oxygen species (ROS). In addition, the combination treatment of PLB and cisplatin resulted in a synergistic inhibition of TSCC viability, apoptosis, and autophagy by increasing intracellular ROS, which may be achieved by activating JNK and inhibiting AKT/mTOR signaling pathways. Finally, the synergistic treatment was also demonstrated in vivo. Therefore, PLB combined with cisplatin is a potential therapeutic strategy against therapy TSCC cisplatin resistance.


PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0120895 ◽  
Author(s):  
Emma Pirilä ◽  
Otto Väyrynen ◽  
Elias Sundquist ◽  
Kaisa Päkkilä ◽  
Pia Nyberg ◽  
...  

2016 ◽  
Vol 36 (2) ◽  
pp. 1143-1149 ◽  
Author(s):  
Jingzhu Zhao ◽  
Chuanxiang Hu ◽  
Jiadong Chi ◽  
Jiansen Li ◽  
Chen Peng ◽  
...  

Author(s):  
Xuechao Jia ◽  
Chuntian Huang ◽  
Yamei Hu ◽  
Qiong Wu ◽  
Fangfang Liu ◽  
...  

Abstract Background Esophageal squamous cell carcinoma (ESCC) is an aggressive and lethal cancer with a low 5 year survival rate. Identification of new therapeutic targets and its inhibitors remain essential for ESCC prevention and treatment. Methods TYK2 protein levels were checked by immunohistochemistry. The function of TYK2 in cell proliferation was investigated by MTT [(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and anchorage-independent cell growth. Computer docking, pull-down assay, surface plasmon resonance, and kinase assay were used to confirm the binding and inhibition of TYK2 by cirsiliol. Cell proliferation, western blot and patient-derived xenograft tumor model were used to determine the inhibitory effects and mechanism of cirsiliol in ESCC. Results TYK2 was overexpressed and served as an oncogene in ESCC. Cirsiliol could bind with TYK2 and inhibit its activity, thereby decreasing dimer formation and nucleus localization of signal transducer and activator of transcription 3 (STAT3). Cirsiliol could inhibit ESCC growth in vitro and in vivo. Conclusions TYK2 is a potential target in ESCC, and cirsiliol could inhibit ESCC by suppression of TYK2.


2021 ◽  
Vol 27 ◽  
Author(s):  
Cuijuan Qian ◽  
Yisheng Yang ◽  
Tianchen Lan ◽  
Yichao Wang ◽  
Jun Yao

Increasing evidence has displayed critical roles of circular RNAs (circRNAs) in tongue squamous cell carcinoma (TSCC). Hsa_circ_0043265 (circ_0043265) has been identified as a tumor suppressor in various tumors. Nevertheless, the critical roles of circ_0043265 in the initiation and progression of TSCC are yet to be fully elucidated. In our study, RNA and protein expressions were detected via qRT-PCR and Western blot. Cell proliferation, migration and invasion were evaluated via CCK-8 and transwell assays. The interactions between circ_0043265, miR-1243 and SALL1 were analyzed via bioinformatics analyses, RNA pull-down and luciferase assays, respectively. The current study demonstrated that circ_0043265 expression was downmodulated in TSCC tissues and cell lines (SCC25, SCC15, SCC9 and Cal27). Functionally, circ_0043265 overexpression led to an attenuation of cell proliferation, migration and invasion of SCC25 and Cal27 cells. Mechanistically, circ_0043265 acted as a competing endogenous RNA (ceRNA) via competitively sponging miR-1243, and restoration of miR-1243 rescued the inhibitory effects of circ_0043265 on cell proliferation, migration and invasion of SCC25 and Cal27 cells. Finally, it was observed that spalt like transcription factor 1 (SALL1), a potential target of miR-1243, was positively modulated via circ_0043265 in SCC25 and Cal27 cells, and SALL1 knockdown reversed the inhibitory effects of circ_0043265 on SCC25 and Cal27 cells. Collectively, the current study demonstrated that circ_0043265 was downmodulated in TSCC and was identified as a ceRNA that restrained the cell proliferation, migration and invasion of SCC25 and Cal27 cells via modulating the miR-1243/SALL1 axis.


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