Proliferation Of Squamous Cell Carcinoma Research Articles

P120-catenin suppresses proliferation and tumor growth of oral squamous cell carcinoma via inhibiting nuclear phospholipase C-γ1 signaling.

p120-catenin (p120) serves as a stabilizer of the calcium-dependent cadherin-catenin complex and loss of p120 expression has been observed in several types of human cancers. The p120-dependent E-cadherin-β-catenin complex has been shown to mediate calcium-induced keratinocyte differentiation via inducing activation of plasma membrane phospholipase C-γ1 (PLC-γ1). On the other hand, PLC-γ1 has been shown to interact with phosphatidylinositol 3-kinase enhancerin the nucleus and plays a critical role in epidermal growth factor-induced proliferation of oral squamous cell carcinoma (OSCC) cells. To determine whether p120 suppresses OSCC proliferation and tumor growth via inhibiting PLC-γ1, we examined effects of p120 knockdown or p120 and PLC-γ1 double knockdown on proliferation of cultured OSCC cells and tumor growth in xenograft OSCC in mice. The results showed that knockdown of p120 reduced levels of PLC-γ1 in the plasma membrane and increased levels of PLC-γ1 and its signaling in the nucleus in OSCC cells and OSCC cell proliferation as well as xenograft OSCC tumor growth. However, double knockdown of p120 and PLC-γ1 or knockdown of PLC-γ1 alone did not have any effect. Immunohistochemical analysis of OSCC tissue from patients showed a lower expression level of p120 and a higher expression level of PLC-γ1 compared withthat of adjacent noncancerous tissue. These data indicate that p120 suppresses OSCC cell proliferation and tumor growth by inhibiting signaling mediated by nuclear PLC-γ1.

Upregulation of far upstream element-binding protein 1 (FUBP1) promotes tumor proliferation and unfavorable prognosis in tongue squamous cell carcinoma.

A well-known transcriptional regulator of the proto-oncogene c-Myc, far-upstream element (FUSE) binding protein 1 (FUBP1) has been demonstrated by previous work to be aberrantly expressed in lots of cancers and plays a critical role in tumor progression; however, its expression and function in tongue squamous cell carcinoma (TSCC) remains unclear. Evaluations with immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to assess FUBP1 expression. The correlations of FUBP1 expression levels with various clinicopathological factors were evaluated with univariate and multivariate analyses. In addition, the role of FUBP1 in TSCC proliferation was studied in TSCC cells by silencing FUBP1. The role of FUBP1 on proliferation and apoptosis was confirmed by cell counting Kit-8, colony formation, cell cycle, and cell apoptosis assays. Immunohistochemistry, qRT-PCR and Western blot results showed FUBP1 expression was higher in TSCC tissues in comparison with adjacent non-cancerous tissues (P <0.05), as well as in patients with advanced-stage disease or cervical lymph node metastasis (P<0.001). The 5-year survival rate was significantly lower in the group with high FUBP1 expression than in that with low FUBP1 expression (P=0.035). FUBP1 expression was also an independent predictor for overall survival in TSCC patients, and was closely related to poor prognosis. FUBP1 knockdown inhibited cancer cell proliferation, and induced cell cycle arrest and apoptosis. FUBP1 was overexpressed in TSCC, and correlated with TSCC cell proliferation and poor prognosis. FUBP1 appears to act as a potential oncogene in TSCC, and may be considered a novel biomarker for TSCC.

WNT1, a target of miR-34a, promotes cervical squamous cell carcinoma proliferation and invasion by induction of an E-P cadherin switch via the WNT/\u03b2-catenin pathway

PurposePersistent infection with high-risk human papillomavirus (HR-HPV) is thought to play a prominent role in the initiation and progression of almost all cases of cervical cancer. Previously, we and others found that microRNA 34a (miR-34a) may be regulated by HR-HPV E6 to contribute to the development of cervical cancer. Here, we aimed to identify the oncogenic potential and clinical significance of a known miR-34a target, WNT1, in cervical squamous cell carcinoma (SCC) development and to investigate the associated mechanisms underlying cervical SCC cell proliferation and invasion.MethodsWNT1 and miR-34a expression levels were assessed in primary cervical lesions using immunohistochemistry and qRT-PCR, respectively. The cellular effects and the expression of its associated genes were examined in cervical SCC-derived Siha and Caski cells after siRNA-WNT1 (downregulation) or miR-34a mimic (upregulation) treatment. A cervical SCC xenograft mouse model was used to investigate the in vivo effects of miR-34a overexpression. HPV-16 E6/E7 expression was inhibited by gene promoter siRNA targeting, after which the levels of miR-34a and WNT1 were examined.ResultsWNT1 protein upregulation was found to be associated with a poor prognosis in cervical SCC patients. In vitro assays in Siha and Caski cells revealed that WNT1 downregulation decreased cell proliferation and invasion, inhibited WNT/β-catenin activation and affected the expression of E-cadherin and P-cadherin. MiR-34a upregulation resulted in decreased WNT1 expression. An inverse correlation between miR-34a and WNT1 expression was also observed in primary cervical SCC tissues. In addition, we found that MiR-34a could regulate an E-cadherin to P-cadherin switch (E-P cadherin switch) to inhibit cell proliferation and tumorigenesis in vitro and in vivo via inactivation of the WNT1/β-catenin pathway. Finally, we found that decreased HPV-16 E6/E7 expression resulted in miR-34a upregulation and WNT1 downregulation in Siha and Caski cells.ConclusionsFrom our results we conclude that WNT1, as a target of miR-34a, can promote cervical SCC cell proliferation and invasion by induction of an E-P cadherin switch via the WNT1/β-catenin pathway. Our results may provide new options for the treatment of patients with cervical SCC.

TWEAK Promotes the Proliferation of Squamous Cell Carcinoma Cells Through Activating cIAP1 Signals.

Recent studies showed that tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) induces the proliferation of squamous cell carcinoma (SCC) cells. However, the precise mechanism underlying such effect of TWEAK remains unclear. This study was designed to elucidate the role of cellular inhibitor of apoptosis 1 (cIAP1) in TWEAK-induced proliferation of SCC cells. Human SCC cells (SCC-13, A431, and SCC-9) were cultured in vitro, receiving the stimulation of TWEAK or TNF-related apoptosis-inducing ligand (TRAIL). We found that TWEAK induced cytoplasmic cIAP1 importation and RIP1 ubiquitination in cells, followed by the activation of canonical nuclear factor kappa B signals. MV1, a cIAP1 inhibitor, abrogated TWEAK-induced proliferation of these cells. Moreover, the interaction between TWEAK and its receptor, fibroblast growth factor-inducible 14 (Fn14), enhanced the expression of TRAIL receptor types 3 and 4 (TRAIL-R3/4). Furthermore, the transfection of TRAIL-R3/4 siRNA abrogated the promotion effect of TWEAK on SCC-13 cell proliferation and cIAP1 expression. Therefore, TWEAK/Fn14 interaction promotes the proliferation of SCC cells through activating cIAP1 signals. Targeting the downstream cIAP1 signals might attenuate the effect of TWEAK on SCC cells.

MiR-30a-5p Inhibits Proliferation and Migration of Lung Squamous Cell Carcinoma Cells by Targeting FOXD1.

Objective To investigate the mechanism of miR-30a-5p inhibiting proliferation and migration of lung squamous cell carcinoma (LSCC) cells by targeting FOXD1. Methods Bioinformatics was used to analyze differentially expressed genes in the TCGA_LUSC database. qRT-PCR was used to detect the expression levels of miR-30a-5p and FOXD1 in human normal lung epithelial cell line and human LSCC cell lines. The protein expression of FOXD1 was detected by western blot. The cell viability and colony formation abilities were examined by CCK-8 and colony formation assays, respectively. Wound healing and Transwell assays were performed to examine the migration and invasion abilities of cells. The targeted binding sites of miR-30a-5p and FOXD1 were predicted by bioinformatics, and dual luciferase assay was used to verify the targeted binding relationship between miR-30a-5p and FOXD1. Result miR-30a-5p was downregulated in LSCC tissues and cells, while FOXD1 was highly expressed. Overexpression of miR-30a-5p or silencing FOXD1 inhibited cell viability, colony formation ability, migration, and invasion of LSCC cells. miR-30a-5p inhibited the proliferation and migration of LSCC cells by downregulating the expression of FOXD1. Conclusion miR-30a-5p can downregulate the expression of FOXD1 and inhibit the proliferation and migration of LSCC.

MicroRNA-330-3p represses the proliferation and invasion of laryngeal squamous cell carcinoma through downregulation of Tra2β-mediated Akt signaling

MicroRNAs (miRNAs), a type of post-transcriptional regulators, exert a crucial role in the malignant progression of laryngeal squamous cell carcinoma (LSCC). MicroRNA-330-3p (miR-330-3p), a recently identified tumor-associated miRNA, is implicated in multiple cancers. Yet, the relevance of miR-330-3p in LSCC remains unexplored. The findings of our study demonstrated a lower expression of miR-330-3p in LSCC. Functional assays revealed that upregulation of miR-330-3p marked restricted the proliferation, colony formation and invasion of LSCC cells. Transformer-2 protein homolog beta (Tra2β) was identified as a target gene of miR-330-3p. An inverse correlation between miR-330-3p and Tra2β mRNA expression was evidenced in LSCC specimens. The upregulation of miR-330-3p significantly repressed Tra2β expression and the phosphorylation of the Akt protein. In addition, Tra2β overexpression markedly abrogated the tumor suppressive role of miR-330-3p in LSCC cells. Overall, our results uncovered that miR-330-3p exerted a tumor-inhibition function in LSCC through targeting Tra2β to inhibit Akt activation.

Effect of miR-204-5p on the proliferation, migration, and invasion on tongue squamous cell carcinoma SCC25 cells by targeting bromodomain-containing protein 4

This study aimed to explore the target relationship between miR-204-5p and bromodomain-containing protein (BRD) 4, as well as their effects on cell proliferation, migration, and invasion in tongue squamous cell carcinoma SCC25. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to detect miR-204-5p and BRD4 expression levels in tongue squamous cell carcinoma and different cell lines. TargetScan and dual luciferase reporter assay were used to confirm the target relationship between miR-204-5p and BRD4. The effects of miR-204-5p on SCC25 cell proliferation were examined by cell counting kit (CCK) 8 assay, whereas those on SCC25 cell migration and invasion were determined by Transwell assay. RT-qPCR and Western blot were used to detect the effects of miR-204-5p mimics and inhibitors on BRD4 expression. Transwell and CCK8 assays were used to detect the effects of miR-204-5p on proliferation, migration, and invasion through BRD4 regulation. miR-204-5p was significantly downregulated in the tissues and cells of squamous cell carcinoma, and BRD4 showed the opposite result. The increase in miR-204-5p expression can inhibit the proliferation, migration, and invasion of SCC25 cells. TargetScan and luciferase test confirmed that miR-204-5p and BRD4 had a negative regulatory relationship with BRD4, respectively. Moreover, miR-204-5p mimics can inhibit BRD4 expression, and miR-204-5p inhibitors can promote BRD4 expression upregulation. When miR-204-5p and BRD4 were overexpressed in SCC25 cells, BRD4 can make up for the inhibitory effect of miR-204-5p on SCC25 cells. miR-204-5p could inhibit proliferation, migration and invasion in tongue squamous cell carcinoma SCC25 cells by targeting BRD4 gene.

B4GALNT1 enhances cell proliferation and growth in oral squamous cell carcinoma via p38 and JNK MAPK pathway.

BackgroundBeta-1,4-N-Acetyl-Galactosaminyltransferase 1 (B4GALNT1) was reported to play an important role in the development of the central nervous systems. We found higher expression of B4GALNT1 in oral squamous cell carcinoma (OSCC) tissues compared to the paired normal adjacent tissues in the TCGA database. This study aimed to investigate whether there was a potential relationship between B4GALNT1 and OSCC tumorigenesis and further explored the possible regulation mechanism.MethodsGene expression level was analyzed by means of real-time quantitative PCR and further cell function experiments were performed including cell proliferation and apoptosis test, cell cycle distribution detection after silencing B4GALNT1 by transfection with B4GALNT1-shRNA lentivirus. Western Blotting was carried out to explore the possible molecular mechanism.ResultsThe present study confirmed the overexpression of B4GALNT1 in OSCC. Compared to the control group, cell proliferation after silencing B4GALNT1 was significantly inhibited and cell apoptosis percentage was significantly higher. Besides, the knockdown of B4GALNT1 resulted in cell cycle arrest at G1 phase in our experiment.ConclusionsB4GALNT1 enhances the proliferation and suppress the apoptosis of OSCC cells probably through JNK and p38 signaling pathway.

RYBP inhibits esophageal squamous cell carcinoma proliferation through downregulating CDC6 and CDC45 in G1-S phase transition process

AimsRING1 and YY1-binding protein (RYBP) is an epigenetic regulator and plays crucial roles in embryonic development. The anti-tumor effect of RYBP has been reported in several cancers recently, but the role of RYBP in esophageal squamous cell carcinoma (ESCC) has not been fully elucidated. The present study aimed to investigate the biological function and the underlying molecular mechanisms of RYBP in ESCC. Materials and methodsWe detected the expression of RYBP in ESCC tissue microarrays (TMA) by immunohistochemistry. Cell proliferation was assessed by CCK8 and colony formation assays. Cell cycle was analyzed by flow cytometry. Gene expression was determined by transcriptome arrays, quantitative real-time PCR (qRT-PCR) and Western blot. Four-week-old male nude mice were used to evaluate the effect of RYBP in ESCC growth. Key findingsWe found that RYBP was downregulated in ESCC compared with adjacent normal tissues. A high level of RYBP expression predicted a better outcome of ESCC patients. Furthermore, overexpression of RYBP inhibited ESCC growth both in vitro and in vivo. Transcriptome arrays and functional studies showed that RYBP decreased the expression of genes related to cell cycles, especially CDC6 and CDC45, which were essential to initiate the DNA replication and G1-S transition. SignificanceTaken together, our study suggests that RYBP suppresses ESCC proliferation by downregulating CDC6 and CDC45, thus inhibiting the G1-S transition.

Long noncoding RNA AGPG regulates PFKFB3-mediated tumor glycolytic reprogramming

Tumor cells often reprogram their metabolism for rapid proliferation. The roles of long noncoding RNAs (lncRNAs) in metabolism remodeling and the underlying mechanisms remain elusive. Through screening, we found that the lncRNA Actin Gamma 1 Pseudogene (AGPG) is required for increased glycolysis activity and cell proliferation in esophageal squamous cell carcinoma (ESCC). Mechanistically, AGPG binds to and stabilizes 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). By preventing APC/C-mediated ubiquitination, AGPG protects PFKFB3 from proteasomal degradation, leading to the accumulation of PFKFB3 in cancer cells, which subsequently activates glycolytic flux and promotes cell cycle progression. AGPG is also a transcriptional target of p53; loss or mutation of TP53 triggers the marked upregulation of AGPG. Notably, inhibiting AGPG dramatically impaired tumor growth in patient-derived xenograft (PDX) models. Clinically, AGPG is highly expressed in many cancers, and high AGPG expression levels are correlated with poor prognosis, suggesting that AGPG is a potential biomarker and cancer therapeutic target.

DJ‑1 promotes cell proliferation and tumor metastasis in esophageal squamous cell carcinoma via the Wnt/β‑catenin signaling pathway.

DJ-1, an oncogene, has been reported to be an independent prognostic indicator of poor survival in patients with esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate the role of DJ-1 in tumor cell proliferation and invasion in ESCC and its underlying mechanisms. It was observed that the expression level of DJ-1 was upregulated and positively associated with EMT biomarkers in 84 human ESCC tissue specimens. Overexpression and knockdown experiments demonstrated that DJ-1 was involved in proliferation, migration, invasion and EMT in ECA-109 cells in vitro and extensive peritoneal seeding in a peritoneal dissemination mice model. Furthermore, the present data revealed that DJ-1 could activate the Wnt/β-catenin signaling pathway, which mediates the EMT and metastasis in ESCC. In conclusions, DJ-1 promoted proliferation, invasion, metastasis and the EMT in ESCC via activation of the Wnt/β-catenin signal pathway. The present results suggested DJ-1 could represent a promising therapeutic target for the prevention and treatment of ESCC-related metastasis.

LncRNA-IUR up-regulates PTEN by sponging miR-21 to regulate cancer cell proliferation and apoptosis in esophageal squamous cell carcinoma.

Imatinib-up-regulated lncRNA (lncRNA-IUR) is a recently identified tumor suppressor, while its role in ESCC is unknown. This study aimed to investigate the role of lncRNA-IUR in esophageal squamous cell carcinoma (ESCC). Between April 2011 and April 2014, the Second Hospital of Jilin University admitted a total of 98 ESCC patients, from whom the present study selected 50 cases (33 males and 17 females; 43-67years; 54.8 ± 6.0year). ESCC cells and transient transfections, qPCR, RNA interaction analysis, western blot, CCK-8 assay, and cell apoptosis analysis were applied. We found that IUR was down-regulated in ESCC, and low levels of IUR predicted poor survival of ESCC patients. In ESCC cells, IUR expression levels were significantly and positively correlated with PTEN mRNA. Bioinformatics analysis showed that IUR may sponge miR-21, which can target PTEN. In ESCC cells, IUR over-expression led to the increased expression levels of PTEN; while miR-21 over-expression led to decreased expression levels of PTEN. IUR and miR-21 failed to affect each other. Cell proliferation and apoptosis analysis showed that IUR and PTEN over-expression inhibited cancer cell proliferation and promoted apoptosis; while miR-21 over-expression played an opposite role. In addition, miR-21 over-expression attenuated the effects of IUR over-expression on PTEN expression and cell proliferation. Therefore, IUR may up-regulate PTEN by sponging miR-21 to regulate cancer cell proliferation and apoptosis in ESCC.

Eldecalcitol (ED-71)-induced exosomal miR-6887-5p suppresses squamous cell carcinoma cell growth by targeting heparin-binding protein 17/fibroblast growth factor-binding protein-1 (HBp17/FGFBP-1).

Heparin-binding protein 17/fibroblast growth factor-binding protein-1 (HBp17/FGFBP-1) was purified from A431 cell-conditioned media based on its capacity to bind to fibroblast growth factor 1 and 2 (FGF-1 and FGF-2). HBp17/FGFBP-1 has been observed to induce the tumorigenic potential of epithelial cells and is highly expressed in oral cancer cell lines and tissues. HBp17/FGFBP-1 is also recognized as a pro-angiogenic molecule as a consequence of its interaction with FGF-2. We have previously reported that Eldecalcitol (ED-71), an analog of 1α,25(OH)2D3, downregulated the expression of HBp17/FGFBP-1 and inhibited the proliferation of squamous cell carcinoma (SCC) cells in vitro and in vivo through NF-κb inhibition. To explore the possibility of microRNA (miRNA) control of HBp17/FGFBP-1, we analyzed exosomal miRNAs from medium conditioned by A431 cells treated with ED-71. Microarray analysis revealed that 12 exosomal miRNAs were upregulated in ED-71-treated A431 cells. Among them, miR-6887-5p was identified to have a predicted mRNA target matching the 3' untranslated region (3'-UTR) of HBp17/FGFBP-1. The 3'-UTR of HBp17/FGFBP-1 was confirmed to be a direct target of miR-6887-5p in SCC/OSCC cells, as assessed with a luciferase reporter assay. Functional assessment revealed that overexpression of miR-6887-5p in SCC/OSCC cells inhibited cell proliferation and colony formation in vitro, and inhibited tumor growth in vivo compared with control. In conclusion, our present study supports a novel anti-cancer mechanism involving the regulation of HBp17/FGFBP-1 function by exosomal miR-6887-5p in SCC/OSCC cells, which has potential utility as a miRNA-based cancer therapy.

Long non-coding RNA BANCR promotes proliferation and migration in oral squamous cell carcinoma via MAPK signaling pathway.

Long non-coding RNAs (lncRNAs) have been shown to be aberrantly expressed in oral squamous cell carcinoma (OSCC), but the biological role and function of BRAF-activated long non-coding RNA (BANCR) in OSCC remain poorly understood. In this study, we found that the expression of BANCR was upregulated in OSCC tissues and cell lines compared to the negative control. The decreased expression of BANCR in vitro markedly inhibited OSCC cell proliferation, migration, and invasion while the opposite was observed for the overexpression of BANCR. The results also showed that the expression of MAPK signaling-related proteins (p-erk, p-akt, and p-p-38) was positively correlated with that of BANCR. Thus, BANCR may play an important role in the tumorigenesis of OSCC, as well as cell proliferation, migration, and invasion of OSCC, and it may be a potential therapeutic target and prognostic factor in OSCC patients.

Linc01234 promotes cell proliferation and metastasis in oral squamous cell carcinoma via miR-433/PAK4 axis

BackgroundIncreasing studies have demonstrated that long non-coding RNAs (lncRNAs) play an important role in tumor progression. However, the potential biological functions and clinical importance of Linc01234 in oral squamous cell carcinoma (OSCC) remain unclear.MethodsWe evaluated the expression profile and prognostic value of Linc01234 in OSCC tissues by RT-qPCR. Then, functional in vitro experiments were performed to investigate the effects of Linc01234 on tumor growth, migration and invasion in OSCC. Mechanistically, RT-qPCR, bioinformatic analysis and dual luciferase reporter assays were performed to identify a competitive endogenous RNA (ceRNA) mechanism involving Linc01234, miR-433-3p and PAK4.ResultsWe found that Linc01234 was clearly upregulated in OSCC tissues and cell lines, and its level was positively associated with T stage, lymph node metastasis, differentiation and poor prognosis of patients with OSCC. Our results shown that Linc01234 inhibited cell proliferation and metastatic abilities in CAL27 and SCC25 cells following its knockdown. Mechanistic analysis indicated that Linc01234 may act as a ceRNA (competing endogenous RNA) of miR-433-3p to relieve the repressive effect of miR-433-3p on its target PAK4.ConclusionsOur results indicated that Linc01234 promotes OSCC progression through the Linc01234/miR-433/PAK4 axis and might be a potential therapeutic target for OSCC.

LncRNA MCM3AP-AS1 inhibits cell proliferation in cervical squamous cell carcinoma by down-regulating miRNA-93

Background: MCM3AP antisense RNA 1 (MCM3AP-AS1) is characterized as an oncogenic lncRNA in hepatocellular carcinoma and glioblastoma. We analyzed TCGA dataset and observed the down-regulation of MCM3AP-AS1 in cervical squamous cell carcinoma (CSCC). The present study was therefore performed to investigate the role of MCM3AP-AS1 in CSCC.Methods: A total of 64 female patients with CSCC (38–68 years old; mean age: 53.1 ± 6.5 years old) were enrolled in the present study. RT-qPCR was performed to evaluate gene expression. Methylation specific PCR (MSP) was performed to assess the methylation of miR-93 gene after the overexpression and silencing of MCM3AP-AS1. Cell transfections were performed to investigate the interactions between MCM3AP-AS1 and miR-93. Cell proliferation was assessed by CCK-8 assay.Results: The results showed that MCM3AP-AS1 was down-regulated in CSCC and predicted poor survival. The expression levels of MCM3AP-AS1 were inversely correlated with the expression levels of miR-93. Overexpression of MCM3AP-AS1 led to down-regulation of miR-93, while silencing of MCM3AP-AS1 played an opposite role in CSCC cells. Methylation-specific PCR revealed that MCM3AP-AS1 could positively regulate the methylation of miR-93 gene. Cell proliferation analysis showed that overexpression of MCM3AP-AS1 led to reduced proliferation rate of CSCC cells. Silencing of MCM3AP-AS1 played an opposite role and overexpression of miR-93 reduced the effects of overexpressing MCM3AP-AS1.Conclusions: Therefore, MCM3AP-AS1 may inhibit cell proliferation in CSCC by down-regulating miRNA-93.

Exosomal Sonic Hedgehog derived from cancer-associated fibroblasts promotes proliferation and migration of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common and aggressive malignancies in China. Cancer‐associated fibroblasts (CAFs) can actively communicate with and stimulate tumor cells, thereby contributing to the development and progression of tumors. Yet, whether CAFs‐derived exosomes have a role in the progression of ESCC is largely unknown. Here, we find that Sonic Hedgehog (SHH) is highly expressed in CAFs lysis solution, conditioned medium of cultured CAFs (CAF‐CM) and CAFs‐derived exosomes, and esophageal cancer cell lines educated by CAF‐CM and CAFs‐derived exosomes can improve their growth and migration abilities in vitro and in vivo. Besides, those effects can be partly neutralized by cyclopamine, inhibitor of the Hedgehog signaling pathway. Thus, our research elucidates the crucial role of CAFs‐derived exosomes in the growth and progression of ESCC, and may open up new avenues in the treatment of ESCC.

Activation of NLRP3 inflammasome promotes the proliferation and migration of esophageal squamous cell carcinoma.

Inflammasomes can identify endogenous danger signals as an inflammatory immune response. As the most common inflammasome, the NLR pyrin family domain containing 3 (NLRP3) inflammasome is associated with the pathogenesis of different tumors. However, the function of the NLRP3 inflammasome in esophageal cancer (EC) has rarely been reported. Herein, the expression levels of the components of NLRP3 inflammasome and Ki-67 were analyzed by immunohistochemistry. Furthermore, correlations between the NLRP3 inflammasome and Ki-67 along with the clinicopathological features of EC patients were evaluated. The components of the NLRP3 inflammasome were also assessed by western blot analysis and quantitative PCR. NLRP3 was silenced or overexpressed in different esophageal squamous cell carcinoma (ESCC) cell lines, and cell viability, migration and invasion were assessed by CCK-8 and Transwell assays. The present results showed that high NLRP3 expression in the tumor specimens was significantly associated with TNM stage and T category. Spearman's correlation analysis revealed a positive correlation between NLRP3 and the Ki-67 proliferation index. The mRNA and protein levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cleaved caspase-1, and interleukin (IL)-1β in tumor tissues were higher than those in non-cancerous tissues. The level of secreted IL-1β in tumor tissues was also increased, as compared to that in normal tissues. Silencing of NLRP3 in KYSE-70 and TE13 cells strongly attenuated cell viability, decreased cell mobility in wound-healing assays and greatly diminished the ability of cell migration and invasion in the Transwell system. Overexpression of NLRP3 in KYSE-510 and EC9706 cells markedly promoted the proliferation, migration and invasion. Collectively, these results revealed that the the NLRP3 inflammasome is upregulated in human ESCC tissues and promotes ESCC progression. Hence, NLRP3 could be a promising new candidate diagnostic and prognostic target.

FTO promotes cell proliferation and migration in esophageal squamous cell carcinoma through up-regulation of MMP13

FTO, a demethylase for N6-methyladenosine (m6A) modification, has been implicated in multiple tumors. However, its roles in esophageal squamous cell carcinoma (ESCC) remain uncovered. This study aims to evaluate the clinical relevance and functional roles in this disease. Through immunohistochemistry, qRT-PCR and Western blot analyses, we found FTO expression in ESCC tissues was stronger than that in adjacent normal tissues, and the survival curves displayed high FTO expression had a trend toward poor prognosis. Functionally, silencing of FTO inhibited ESCC cell growth and migration in CCK8, EdU, colony formation and transwell assays and FTO overexpression showed the opposite results. Furthermore, FTO was also required for the tumorigenicity of ESCC cells in nude mice. The data from RNA-seq analysis revealed that MMP13 expression was significantly affected by FTO knockdown. qRT-PCR and Western blot assays confirmed that MMP13 was positively regulated by FTO in both mRNA and protein levels. Additionally, the functional link between FTO and MMP13 was explored by CCK8 and transwell chamber approaches. These findings suggest that FTO is up-regulated and plays oncogenic roles in ESCC. MMP13 may function as a downstream target of FTO.

MiR-936 Suppresses Cell Proliferation, Invasion, and Drug Resistance of Laryngeal Squamous Cell Carcinoma and Targets GPR78.

MicroRNAs (miRs) play important roles in tumor progression. miR-936 has been reported to suppress cell invasion and proliferation of glioma and non-small cell lung cancer. Nevertheless, the function of miR-936 in laryngeal squamous cell carcinoma (LSCC) remains undiscovered. Hence, our study was to investigate the role of miR-936 in LSCC. In our present research, we have testified that miR-936 was substantially downregulated in LSCC tissues compared with adjacent normal tissues. Furthermore, miR-936 could inhibit proliferation, migration and invasion, and improve the sensitivity to doxorubicin and cisplatin of LSCC cells. Additionally, luciferase reporter assays were performed to confirm that GPR78 was a novel target of miR-936, and the protein expression of GPR78 was obviously inhibited by miR-936 in LSCC cells. In summary, our study indicates that the miR-936/GPR78 axis could be both a diagnostic marker and a therapeutic target for LSCC.