scholarly journals PKD3 promotes metastasis and growth of oral squamous cell carcinoma through positive feedback regulation with PD-L1 and activation of ERK -STAT1/3-EMT signaling

2020 ◽  
Author(s):  
Bomiao Cui ◽  
Jiao Chen ◽  
Min Luo ◽  
Yiying Liu ◽  
Hongli Chen ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Tumor Growth ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Positive Feedback ◽  
Feedback Regulation ◽  
Mesenchymal Transition ◽  
Epithelial Markers

Abstract Background: Oral squamous cell carcinoma (OSCC) has a high incidence of metastasis. Tumor immunotherapy targeting programmed death ligand 1 (PD-L1) or programmed cell death protein 1 (PD-1) is revolutionary; however, only a few patients with OSCC respond to this treatment. Therefore, it is necessary to understand the molecular mechanisms of OSCC growth and metastasis to identify new therapeutic targets. Methods: In this study, we first analyzed the expression level of protein kinase D3 (PKD3) and PD-L1, and their correlation with mesenchymal and epithelial markers through UALCAN database, UCSC Xena, western blot, and immunostaining of human OSCC tissue sections. We knocked down and overexpressed PKD3 in OSCC cell lines and analyzed cell growth, migration, and invasion using western blot, cell proliferation assays, wound healing assays, and Transwell assays. A mouse footpad xenograft model was used to study the effects of PKD3 on tumor growth and lymph node metastasis in vivo. Results: The expression of PKD3 and PD-L1 in OSCC cells and tissues was significantly increased, and correlated positively with mesenchymal markers but negatively with epithelial markers. Silencing PKD3 significantly inhibited the growth, metastasis, and invasion of OSCC cells, while its overexpression promoted these processes. PKD3 regulated PD-L1 expression through the ERK/STAT1/3 signaling pathway, forming a positive feedback regulatory loop with PD-L1 to induce epithelial-mesenchymal transition (EMT) in OSCC. Conclusions: There is a positive feedback regulation between PKD3 and PD-L1, which can drive the EMT of OSCC cells through the ERK/STAT1/3 pathway, thereby promoting tumor growth and metastasis. Our findings provide a theoretical basis for targeting PKD3 as an alternative method to block EMT for regulating PD-L1 expression and inhibiting OSCC growth and metastasis . Keywords: OSCC, PKD3, PD-L1, EMT, tumor growth, metastasis

scholarly journals PKD3 promotes metastasis and growth of oral squamous cell carcinoma through positive feedback regulation with PD-L1 and activation of ERK-STAT1/3-EMT signalling

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Bomiao Cui ◽  
Jiao Chen ◽  
Min Luo ◽  
Yiying Liu ◽  
Hongli Chen ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Positive Feedback ◽  
Molecular Mechanisms ◽  
Xenograft Model ◽  
Feedback Regulation ◽  
Epithelial Markers ◽  
High Incidence

AbstractOral squamous cell carcinoma (OSCC) has a high incidence of metastasis. Tumour immunotherapy targeting PD-L1 or PD-1 has been revolutionary; however, only a few patients with OSCC respond to this treatment. Therefore, it is essential to gain insights into the molecular mechanisms underlying the growth and metastasis of OSCC. In this study, we analysed the expression levels of protein kinase D3 (PKD3) and PD-L1 and their correlation with the expression of mesenchymal and epithelial markers. We found that the expression of PKD3 and PD-L1 in OSCC cells and tissues was significantly increased, which correlated positively with that of mesenchymal markers but negatively with that of epithelial markers. Silencing PKD3 significantly inhibited the growth, metastasis and invasion of OSCC cells, while its overexpression promoted these processes. Our further analyses revealed that there was positive feedback regulation between PKD3 and PD-L1, which could drive EMT of OSCC cells via the ERK/STAT1/3 pathway, thereby promoting tumour growth and metastasis. Furthermore, silencing PKD3 significantly inhibited the expression of PD-L1, and lymph node metastasis of OSCC was investigated with a mouse footpad xenograft model. Thus, our findings provide a theoretical basis for targeting PKD3 as an alternative method to block EMT for regulating PD-L1 expression and inhibiting OSCC growth and metastasis.

scholarly journals Evaluation of Hyaluronic Acid to Modulate Oral Squamous Cell Carcinoma Growth In Vitro

2020 ◽  
Vol 11 (4) ◽  
pp. 72
Author(s):  
Jordan Ringer ◽  
Bryan Morrison ◽  
Karl Kingsley
Keyword(s):  
Growth Rate ◽  
Squamous Cell Carcinoma ◽  
Hyaluronic Acid ◽  
Oral Squamous Cell Carcinoma ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Chemotherapeutic Agents ◽  
Oral Tumor

Introduction: Previous studies have demonstrated that glycosaminoglycan hyaluronic acid (HA) is capable of mediating oral tumor growth. Some clinical evidence has suggested reduced HA expression predicts poor cancer prognosis and that HA-chemotherapy conjugates may function synergistically to inhibit oral tumor growth. Other studies have found conflicting results that suggest enhanced CD44-HA-mediated growth and proliferation. Due to the lack of clarity regarding HA function, the primary goal of this study was to investigate the effects of HA using well-characterized oral cancer cell lines. Methods: Using several commercially available oral squamous cell carcinoma lines (and a normal non-cancerous control), 96-well growth and viability assays were conducted using HA (alone and in combination with chemotherapeutic agents paclitaxel and PD98059). Results: Different results were observed in each of the cell lines evaluated. HA induced small, non-significant changes in cellular viability among each of the cell lines within a narrow range (1–8%), p = 0.207. However, HA induced differing effects on growth, with minimal, non-significant changes among some cell lines, such as SCC4 (+1.7%), CCL-30 (−2.8%), and SCC15 (−2.5%), p = 0.211 and more robust inhibition among other cell lines, SCC9 (−24.4%), SCC25 (−36.6%), and CAL27 (−47.8%), p = 0.0001. Differing effects were also observed with growth and viability under concomitant administration of HA with PD98059 or paclitaxel. Further analysis of these data revealed strong inverse (Pearson’s) correlations between initial baseline growth rate and responsiveness to HA administration, ranging from R = −0.27 to R = −0.883. Conclusion: The results of this study revealed differing responses to HA, which may be inversely correlated with intrinsic characteristics, such as the baseline growth rate. This may suggest that the more rapidly growing cell lines are more responsive to combination therapy with hyaluronic acid; an important finding that may provide insights into the mechanisms responsible for these observations.

scholarly journals Knockdown of circ_0011946 targets miR-216a-5p/BCL2L2 axis to regulate proliferation, migration, invasion and apoptosis of oral squamous cell carcinoma cells

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Zhou ◽  
Shuhong Zhang ◽  
Zhonghan Min ◽  
Zhongwei Yu ◽  
Huaiwei Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
B Cell Lymphoma ◽  
Luciferase Reporter ◽  
Migration And Invasion

Abstract Background Circular RNAs (circRNAs) are implicated in the development of oral squamous cell carcinoma (OSCC). The aim of current research is to elucidate the role and mechanism of circ_0011946 in the functional behaviors of OSCC cells. Methods Circ_0011946, microRNA (miR)-216a-5p, B cell lymphoma-2-like 2 protein (BCL2L2) abundances were exposed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or western blot. Cell proliferation, migration, invasion and apoptosis were detected by MTT, colony formation assay, transwell, wound-healing and flow cytometry assays, respectively. Target correlation was tested by dual-luciferase reporter and RNA pull-down assays. An in vivo xenograft experiment was employed to investigate the function of circ_0011946 on tumor growth in vivo. Results Circ_0011946 and BCL2L2 levels were increased, while miR-216a-5p level was decreased in OSCC tissues and cells. Circ_0011946 knockdown impeded proliferation, migration, and invasion, but promoted apoptosis in OSCC cells. Circ_0011946 functioned as a sponge for miR-216a-5p, and BCL2L2 was targeted by miR-216a-5p. Besides, miR-216a-5p or BCL2L2 knockdown partly attenuated the inhibitory influences of circ_0011946 silence or miR-216a-5p overexpression on OSCC cell progression. Furthermore, circ_0011946 post-transcriptionally regulated BCL2L2 through sponging miR-216a-5p. Moreover, circ_0011946 knockdown constrained OSCC tumor growth in vivo. Conclusion Circ_0011946 silence repressed OSCC cell proliferation, migration, and invasion, but promoted apoptosis through the regulation of the miR-216a-5p/BCL2L2 axis.

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