Invasion Of Adenocarcinoma Cells Research Articles

GALNT5 promotes migration and invasion of pancreatic ductal adenocarcinoma cells by activating Erk signaling pathway.

Aberrant glycosylation has been implicated in promoting the progression and metastasis of pancreatic ductal adenocarcinoma (PDAC). However, the contribution of different glycosylation-related genes in PDAC remains to be clarified. In this study, we performed a differential analysis of RNA-Seq data from TCGA and GTEx and found GALNT5 as the most significant upregulated glycosylation-related gene in PDAC. Using publicly available single-cell sequencing data, we further revealed that GALNT5 is predominantly expressed in malignant ductal epithelial cells of PDAC. Correlation analysis indicated that GALNT5 is the essential member of the GALNT family associated with poor prognosis of PDAC. Overexpression of GALNT5 in PANC-1 or MIAPaCa-2 cells with low endogenous GALNT5 enhances migration and invasion. Conversely, knockdown of GALNT5 in AsPC-1 cells with high endogenous GALNT5 inhibits migration and invasion. Mechanistically, we discovered that GALNT5 activates the Erk signaling pathway in PDAC. Our findings suggest GALNT5 is a potential therapeutic target for PDAC.

Adipocyte-derived CXCL10 in obesity promotes the migration and invasion of ovarian cancer cells

BackgroundAs a widespread epidemic, obesity poses a significant risk to health and leads to physiological abnormalities, including diabetes mellitus and inflammation. Obesity-induced inflammation can accelerate the development of various cancers; however, the role of obesity in the migration of ovarian carcinoma is still unclear.ResultsTwenty-four commonly upregulated genes were identified from single-cell RNA sequencing datasets of both ovarian carcinoma and adipose tissue of obese humans, with the chemokine CXCL10 showing a significant increase in adipose tissues associated with obesity. And CXCL10 treated primed macrophages exhibit both direct and indirect effects on the proliferation, apoptosis, migration, and invasion of ovarian adenocarcinoma cells. The treatment of CXCL10 on the SKOV3 cells enhances FAK expression and phosphorylation, thereby accelerating the migration and invasion of ovarian cancer cells. Conditioned medium-derived from CXCL10-treated THP-1 cells significantly promoted ovarian cancer cell migration and invasion, which may be attributed to the increased expression of C1QA, C1QC, CCL24, and IL4R in macrophages.ConclusionsObesity exacerbates the production of CXCL10 from adipose tissues in obese women. CXCL10 is a key hub factor between developments of ovarian cancer and adipose tissues in obese. Targeting adipose-derived CXCL10 or its downstream macrophages may be a potential strategy to alleviate ovarian cancer accompanied by obesity.

PARD6A promotes lung adenocarcinoma cell proliferation and invasion through Serpina3.

Par6α encoded by PARD6A is a member of the PAR6 family and is reported to promote cancer initiation and progression. PARD6A is frequently upregulated in different types of cancers, but its regulatory role in lung cancer progression is yet to be established. In this study, we analyzed the PARD6A expression in biopsies from lung adenocarcinoma (LUAD) patients, and the survival probability using LUAD tissue microarray (TMA) and online datasets from TCGA and GEO. We conducted in vitro and in vivo assays to assess the role of PARD6A in regulating lung cancer progression, including proliferation, wound healing, transwell, RNA-seq, and subcutaneous tumor mice models. Our findings revealed that PARD6A is highly expressed in cancer tissues from LUAD patients and is associated with poor prognosis in LUAD patients. In vitro assays showed that PARD6A promoted cell proliferation, migration, and invasion. The transcriptome sequencing identified Serpina3 as one of the key downstream molecules of PARD6A. Ectopic expression of Serpina3 rescued impaired proliferation, migration, and invasion in PARD6A-knocking down H1299 cells, whereas silencing Serpina3 impeded enhanced proliferation, migration, and invasion in PARD6A-overexpressing H1975 cells. Our findings suggest that PARD6A promotes lung cancer progression by inducing Serpina3, which may be a promising therapeutic target.

Detecting haplotype-specific transcript variation in long reads with FLAIR2

BackgroundRNA-seq has brought forth significant discoveries regarding aberrations in RNA processing, implicating these RNA variants in a variety of diseases. Aberrant splicing and single nucleotide variants (SNVs) in RNA have been demonstrated to alter transcript stability, localization, and function. In particular, the upregulation of ADAR, an enzyme that mediates adenosine-to-inosine editing, has been previously linked to an increase in the invasiveness of lung adenocarcinoma cells and associated with splicing regulation. Despite the functional importance of studying splicing and SNVs, the use of short-read RNA-seq has limited the community’s ability to interrogate both forms of RNA variation simultaneously.ResultsWe employ long-read sequencing technology to obtain full-length transcript sequences, elucidating cis-effects of variants on splicing changes at a single molecule level. We develop a computational workflow that augments FLAIR, a tool that calls isoform models expressed in long-read data, to integrate RNA variant calls with the associated isoforms that bear them. We generate nanopore data with high sequence accuracy from H1975 lung adenocarcinoma cells with and without knockdown of ADAR. We apply our workflow to identify key inosine isoform associations to help clarify the prominence of ADAR in tumorigenesis.ConclusionsUltimately, we find that a long-read approach provides valuable insight toward characterizing the relationship between RNA variants and splicing patterns.

Study of the mechanism by which Xiaoyan decoction combined with E7449 regulates tumorigenesis in lung adenocarcinoma.

TNKS is a new target for the treatment of lung adenocarcinoma, the synergistic effects of the TCM compound Xiaoyan decoction and the TNKS inhibitor E7449 in the intervention on TNKS were investigated, and the possible underlying mechanisms involved were clarified. Immunohistochemistry was used to analyse TNKS expression in tumour tissues. The impact of targeting TNKS on cell growth, invasion, apoptosis, key genes and signalling pathways was investigated in tumour cells by Western blotting, rescue experiments, colony formation assays, flow cytometry and label-free experiments. Tumour xenografts with A549 cells were then transplanted for invivo study. We found that TNKS high expression was closely related to the advanced tumour stage and tumour size in lung adenocarcinom. After TNKS was knocked down invitro, the growth, proliferation, migration and invasion were markedly reduced in A549 and H1975 cells. We subsequently applied the Xiaoyan decoction and TNKS inhibitors to intervene in lung adenocarcinoma. Xiaoyan decoction and E7449 suppressed TNKS expression and inhibited adenocarcinoma cell proliferation, migration, invasion and apoptosis invitro. Proteomic analysis revealed that E7449 treatment may be most closely associated with the classic Wnt/β-catenin pathway, whereas Xiaoyan decoction treatment may be related to the WNT/PLAN pathway. Xenograft studies confirmed that E7449 or Xiaoyan decoction inhibited lung tumour growth invivo and attenuated the Wnt signalling pathway in adenocarcinoma. These findings suggest that TNKS is a novel therapeutic target. TCM preparations and small molecule inhibitors are expected to constitute an effective combination strategy.

High LINC00626 expression promotes esophagogastric junction adenocarcinoma metastasis: the mediating role of the JAK1/STAT3/KHSRP axis

To investigate the role of JAK1/STAT3/KHSRP axis in mediating the regulatory effect of LINC00626 on progression of esophagogastric junction adenocarcinoma. We collected surgical tumor and adjacent tissue specimens from 64 patients with esophagogastric junction adenocarcinoma and examined the expression levels of LINC00626 and KHSRP. qRT-PCR was used to detect the expressions of LINC00626 and KHSRP in 6 esophageal adenocarcinoma cell lines (OE-19, TE-7, Bic-1, Flo-1, SK-GT-4, and BE-3) and a normal esophageal epithelial cell line (HET-1A). OE-19 and TE-7 cell lines with stable LINC00626 knockdown and FLO-1 and SK-GT-4 cells stably overexpressing LINC00626 were constructed by lentiviral transfection, and the changes in proliferation, migration and invasion of the cells were evaluated using Cell Counting Kit-8 (CCK-8) assay and Transwell migration/invasion assay. The expressions of KHSRP and JAK/STAT pathway proteins in the transfected cells were detected with Western blotting. The effects of LINC006266 knockdown and overexpression on subcutaneous tumor formation and lung metastasis of OE-19 and FLO-1 cell xenografts were tested in nude mice. The expression levels of LINC00626 and KHSRP were significantly increased in esophagogastric junction adenocarcinoma tissues and in esophageal adenocarcinoma cells. LINC00626 knockdown obviously inhibited the proliferation, migration and invasion of esophageal adenocarcinoma cells in vitro and decreased their tumor formation and lung metastasis abilities in nude mice, while overexpression of LINC00626 produced the opposite effects. In esophageal adenocarcinoma cells, LINC0626 knockdown significantly decreased and LINC00626 overexpression strongly enhanced the phosphorylation of JAK1 and STAT3. High LINC00626 expression promotes esophageal-gastric junction adenocarcinoma metastasis by activating the JAK1/STAT3/KHSRP signal axis.

Cytotoxicity of bismuth(III) dithiocarbamate derivatives by promoting a mitochondrial-dependent apoptotic pathway and suppressing MCF-7 breast adenocarcinoma cell invasion.

We previously reported that the bismuth(III) dithiocarbamate derivative, bismuth diethyldithiocarbamate (1) exhibited greater cytotoxicity while inducing apoptosis via the intrinsic pathway in MCF-7 cells. We further evaluated the other bismuth(III) dithiocarbamate derivatives, Bi[S2CNR]3, with R = (CH2CH2OH)(iPr), (CH2)4, and (CH2CH2OH)(CH3), denoted as 2, 3, and 4, respectively, in the same MCF-7 cell line. 2-4 were found to exhibit IC50 values of 10.33 ± 0.06µM, 1.07 ± 0.01µM and 25.37 ± 0.12µM, respectively, compared to that of cisplatin at 30.53 ± 0.23µM. Apoptotic promotion via the mitochondrial-dependent pathway was due to the elevation of intracellular reactive oxygen species (ROS), promotion of caspases, release of cytochrome c, fragmentation of DNA, and results of staining assay observed in all compound-treated cells. 2-4 are also capable of suppressing MCF-7 cell invasion and modulate Lys-48 also Lys-63 linked polyubiquitination, leading to proteasomal degradation. Analysis of gene expression via qRT-PCR revealed their modulation, which supported all activities conducted upon treatment with 2-4. Altogether, bismuth dithiocarbamate derivatives, with bismuth(III) as the metal center bound to ligands, isopropyl ethanol, pyrrolidine, and methyl ethanol dithiocarbamate, are potential anti-breast cancer agents that induce apoptosis and suppress metastasis. Further studies using other breast cancer cell lines and in vivo studies are recommended to clarify the anticancer effects of these compounds.

GPR109A partly mediates inhibitory effects of β-hydroxybutyric acid on lung adenocarcinoma cell proliferation, migration and invasion

To explore the mechanism that mediates the inhibitory effects of β-hydroxybutyrate (BHB) on lung adenocarcinoma cells. A549 and LLC cell lines treated with 5 or 10 mmol/L BHB were examined for changes in cell viability, proliferation, migration, and invasion using CCK-8 assay, EdU staining, scratch assay, and Transwell assay. The differential expression of GPR109A in lung adenocarcinoma and normal lung tissue was analyzed using GEPIA database. GPR109A expressions in BHB-treated lung adenocarcinoma cells were determined using RT-PCR and Western blotting. The changes in IC50 of BHB were examined in A549 and LLC cells with GPR109A knockdown. The effect of BHB administered via gavage for 21 days on tumor growth was evaluated in nude mouse and Balb/c mouse models bearing xenografts derived A549 and LLC cells with or without GPR109A knockdown. Treatment with BHB concentration-dependently repressed the viability, proliferation, migration and invasion of A549 and LLC cells. GPR109A expression was significantly decreased in lung adenocarcinoma tissues and A549 and LLC cell lines (P<0.05). Loss of function experiments showed that the inhibitory effects of BHB on A549 and LLC cells were partly mediated by GPR109A, and in the tumor-bearing mouse models, BHB significantly inhibited tumor growth partly by regulating GPR109A expression (P<0.05). BHB can repress the malignant behaviors of A549 and LLC cells and inhibit tumor growth in mice, and these effects are mediated partly by regulating GPR109A expression.

CXXC finger protein 1 (CFP1) bridges the reshaping of genomic H3K4me3 signature to the advancement of lung adenocarcinoma

Histone H3 lysine 4 trimethylation (H3K4me3) is a canonical chromatin modification associated with active gene transcription, playing a pivotal role in regulating various cellular functions. Components of the H3K4me3 methyltransferase complex, known as the proteins associated with SET1 (COMPASS), have been implicated in exerting cancer-protective or cancer-inhibitory effects through inducive H3K4me3 modification. However, the role of the indispensable non-catalytic component of COMPASS CXXC-type zinc finger protein 1 (CFP1) in malignant progression remains unclear. We have unveiled that CFP1 promote lung adenocarcinoma (LUAD) cell proliferation, migration, and invasion while impairing cell apoptosis through in vitro and in vivo models. In addition, high CFP1 expression was identified as emerged as an adverse prognostic indicator across multiple public and in-house LUAD datasets. Notably, CFP1 deficiency led to dual effects on cancer cell transcriptome including extensive inactivation of cancer-promoting as well as activation of cancer repressors. Combining this with the chromatin immunoprecipitation sequencing (ChIP-seq) analysis, we showed that CFP1 ablation reshaped the genomic H3K4me3 distribution signature, with prominent effects on TGF-β and WNT signaling pathways. Collectively, our study proposes that CFP1 mediates tumorigenesis by genomic histone methylation reprogramming, offering insights for future investigations into epigenetic modifications in cancer progression and potential therapeutic advancements.

CircRNA PGAM1 Promotes the Migration and Invasion of Pancreatic Adenocarcinoma Cells by Activating the AKT/mTOR Signaling Pathway.

Pancreatic adenocarcinoma (PAAD)is a lethalmalignancy ofthe gastrointestinaltract. Circular RNA, an endogenous noncoding RNA, is considered a new regulatory molecule in tumorigenesis and development. Here, we aimed to investigate the role of circPGAM1 in PAAD. The PAAD cell line HPAC was transfected with OE-circPGAM1 to overexpress circPGAM1 and treated with AZD5363 to inhibit the AKT/mTOR pathway. Simultaneously, another PAAD cell line BxPC-3 was transfected with sh-circPGAM1 to silence circPGAM1. The GEPIA database was used to determine the expression of circPGAM1 in PAAD and its association with overall and disease-free survival. CircPGAM1 expression levels were determined in cell lines using reverse transcription-quantitative PCR. The cell counting kit-8, wound healing, and transwell assays were performed to determine cell migration and invasion. The protein expression levels of phosphorylated AKT and mTOR were determined using western blotting. CircPGAM1 was overexpressedin PAAD and relatedtopoorprognosis. Silencing circPGAM1 inhibited migration and invasion of BxPC-3 cells, and overexpression of circPGAM1 showed the opposite effects. Overall, circPGAM1 promoted the migration and invasion of PAAD cells through the AKT/mTOR axis.

The GLI2/CDH6 axis enhances migration, invasion and mitochondrial fission of stomach adenocarcinoma cells

It has been reported that cadherin 6 (CDH6) upregulation is associated with enhanced epithelial-to-mesenchymal transition (EMT) in several types of solid tumor cells. The current study aimed to explore the effect of CDH6 on the migration and invasion of stomach adenocarcinoma (STAD) cells, the transcription factors involved in CDH6 dysregulation and their effect on mitochondrial fission. Bioinformatics analysis was performed using data extracted from the Genotype-Tissue Expression Project, the Cancer Genome Atlas and Kaplan-Meier plotter. AGS and HGC27 cells were used to establish an in vitro STAD cell model. The results showed that higher CDH6 expression was associated with significantly shorter overall survival in patients with STAD. In addition, CDH6 overexpression promoted wound healing, enhanced the invasion ability of tumor cells and increased mitochondrial fission. Glioma-associated oncogene family zinc finger 2 (GLI2) could bind to the CDH6 promoter and activate its transcription. Fluorescent labeling also showed that GLI2 overexpression promoted mitochondrial fission. However, CDH6 silencing significantly reduced mitochondrial fragmentation. Besides, GLI2 overexpression notably upregulated phosphorylated-focal adhesion kinase and dynamin-related protein 1. However, the above effects were largely abrogated by CDH6 knockdown. In conclusion, the present study suggested that the novel GLI2/CDH6 axis could enhance the migration, invasion and mitochondrial fission of STAD cells.

SAMD4A serves as a negative prognostic marker for gastric cancer patients

IntroductionThe incidence and mortality of gastric cancer remain high in the world. We aim to explore the role of SAMD4A in gastric cancer. MethodsThe expression of SAMD4A was up-regulated in gastric adenocarcinoma and the expression level of SAMD4A in gastric adenocarcinoma and adjacent normal tissues was verified by RT-qPCR. Immunohistochemical showed that SAMD4A was mainly located in the cytoplasm. ResultThe result showed that the expression of SAMD4A was positively correlated with the depth of invasion, the number of lymph node metastasis, and the clinical stage in patients with gastric adenocarcinoma. Survival analysis of GEPIA database showed that the overall survival of gastric adenocarcinoma patients with positive SAMD4A expression was lower than that of the negative group. Gastric cancer cell lines with knockdown of the SAMD4A gene were used to observe the differences in cell proliferation, invasion, and migration abilities between the knockdown group and the control group. The results showed that the proliferation, invasion, and migration abilities of the SAMD4A knockdown group were both weakened compared with the control group. This study is the first to find that the expression level of SAMD4A in gastric cancer is higher than that in the adjacent group and is associated with poor prognosis of patients. SAMD4A promotes the proliferation, invasion, and migration of gastric adenocarcinoma cells. ConclusionThis indicates that SAMD4A plays an important role in the occurrence and development of gastric cancer, and is expected to be an effective indicator for the diagnosis and evaluation of the prognosis of gastric cancer.

Analysis and validation of the potential of the MYO1E gene in pancreatic adenocarcinoma based on a bioinformatics approach.

Pancreatic adenocarcinoma (PAAD) is a common digestive cancer, and its prognosis is poor. Myosin 1E (MYO1E) is a class I myosin family member whose expression and function have not been reported in PAAD. In the present study, bioinformatics analysis was used to explore the expression levels of MYO1E in PAAD and its prognostic value, and the immunological role of MYO1E in PAAD was analyzed. The study revealed that a variety of malignancies have substantially increased MYO1E expression. Further investigation demonstrated that PAAD tissues exhibited greater levels of MYO1E mRNA and protein expression than normal tissues. High MYO1E expression is associated with poor prognosis in patients with PAAD. MYO1E expression was also associated with pathological stage in patients with PAAD. Functional enrichment analysis demonstrated that MYO1E was linked to multiple tumor-related mechanisms in PAAD. The pancreatic adenocarcinoma tumor microenvironment (TME) was analyzed and it was revealed that MYO1E expression was positively associated with tumor immune cell infiltration. In addition, MYO1E was closely associated with some tumor chemokines/receptors and immune checkpoints. In vitro experiments revealed that the suppression of MYO1E expression could inhibit pancreatic adenocarcinoma cell proliferation, invasion and migration. Through preliminary analysis, the present study evaluated the potential function of MYO1E in PAAD and its function in TME, and MYO1E may become a potential biomarker for PAAD.

Nucleophosmin promotes lung adenocarcinoma cell proliferation, migration and invasion by activating the EGFR/MAPK signaling pathway.

Lung adenocarcinoma (LUAD) is the main cause of death globally. The present study investigated the prognostic value and functional verification of nucleophosmin (NPM1) in LUAD. LUAD and normal samples from The Cancer Genome Atlas were analyzed to identify whether NPM1 is associated with LUAD prognosis. NPM1 protein expression level was verified by western blotting. Cell proliferation, migration and invasion were detected by Cell Counting Kit‑8, wound healing and Transwell assays, respectively. EGFR/MAPK pathway‑related proteins [phosphorylated (p)‑EGFR/EGFR, p‑MEK/MEK, and p‑ERK/ERK] expression was measured through western blotting. A xenograft tumor mice model was constructed to perform the invivo verification. NPM1 was upregulated in LUAD cells, and high‑level NPM1 indicated poor prognosis in patients with LUAD. Invitro experiments revealed that NPM1 knockdown inhibited LUAD cell proliferation, migration and invasion. Moreover, protein expression of p‑EGFR/EGFR, p‑MEK/MEK and p‑ERK/ERK was reduced with the NPM1 silencing. Furthermore, EGF, an activator of the EGFR/MAPK pathway, reversed the effects of NPM1. Invivo experiments showed that NPM1 knockdown inhibited tumor growth and protein levels of p‑EGFR/EGFR, p‑MEK/MEK and p‑ERK/ERK. NPM1 is related to the poor prognosis of LUAD and promotes the malignant progression of LUAD by activating the EGFR/MAPK pathway. This discovery provides a new potential therapeutic target for the diagnosis and treatment of LUAD.

Acetylcholine promotes chronic stress-induced lung adenocarcinoma progression via α5-nAChR/FHIT pathway.

Chronic stress significantly elevates the expression levels of various neurotransmitters in the tumour microenvironment, thereby promoting the cell growth and metastasis of lung adenocarcinoma (LUAD). However, the role of chronic stress in the progression of LUAD remains unclear. In this study, we found that chronic restraint stress increases the levels of the neurotransmitter acetylcholine (ACh), and the α5-nicotinic acetylcholine receptor (α5-nAChR) and decreased fragile histidine triad (FHIT) expression in vivo. Crucially, the increased ACh levels promoted LUAD cell migration and invasion via modulation of the α5-nAChR/DNA methyltransferase 1 (DNMT1)/FHIT axis. In a chronic unpredictable stress (CUMS) mouse model, chronic stress promotes tumour development, accompanied by changes in α5-nAChR, DNMT1, FHIT, and vimentin. Together, these findings reveal a novel chronic stress-mediated LUAD signalling pathway: chronic stress enforces lung adenocarcinoma cell invasion and migration via the ACh/α5-nAChR/FHIT axis, which could be a potential therapeutic target for chronic stress-related LUAD.

SPON2 promotes the bone metastasis of lung adenocarcinoma via activation of the NF-κB signaling pathway.

Bone metastasis severely affects the life span and quality of life of survivors of lung adenocarcinoma (ADC). There is a pressing need to identify viable biomarkers for this incurable, fatal disease. Spondin-2 (SPON2) has been reported to be involved in metastasis and cancer progression, but its role in bone metastasis in patients with lung ADC has rarely been studied. Here, we showed that the upregulation of SPON2 increased the migration, invasion, and epithelial-to-mesenchymal transition of ADC cells in vitro, whereas silencing SPON2 repressed these processes. Consistently, silencing SPON2 significantly reduced the bone metastasis of ADC cells in vivo. Mechanistically, SPON2 activated the nuclear factor-κB (NF-κB) signaling pathway and increased the expression levels of MMP2 and MMP9. Blocking NF-κB using an inhibitor attenuated the SPON2-induced migration and invasion of ADC cells. In addition, we found that SPON2 expression levels were increased in metastatic bone tissues compared to primary ADC tissues. The upregulation of SPON2 was positively correlated with MMP2 and MMP9 expression levels in metastatic bone tissues. In conclusion, these results illustrate that SPON2 plays a key role in ADC by activating the NF-κB pathway to promote bone metastasis, which suggests that it may be a target for future drug development.

Down-regulation of FBP1 in lung adenocarcinoma cells promotes proliferation and invasion through SLUG mediated epithelial mesenchymal transformation.

Metabolic reprogramming and epithelial-mesenchymal transformation (EMT) play an important role in lung cancer. In recent studies, metabolic enzymes such as Fructose-1,6-bisphosphatase 1 (FBP1) have shown potential functions beyond regulating metabolism. Western blot assay was performed to detect glycolysis-related and EMT-related protein expression levels. The glucose uptake kit and adenosine triphosphate (ATP) detection kit were used to detect glucose uptake rate and ATP content. Transwell assay was used to determine the invasiveness of lung adenocarcinoma cells. Wound healing assay was used to determine the metastatic ability of lung adenocarcinoma cells. Methyl thiazolyl tetrazolium (MTT) assay and EdU staining were performed to investigate the effect of FBP1 overexpression on lung adenocarcinoma proliferation. Overexpression of FBP1 down-regulated glycolysis-related protein levels and inhibited glucose uptake and ATP production, while knockdown of FBP1 had the opposite effect. Overexpression of FBP1 reversed EMT and inhibited Slug expression. Meanwhile, overexpression of FBP1 impaired the invasion, metastasis and proliferation ability of lung adenocarcinoma cells. In contrast, FBP1 knockdown promoted the EMT process, up-regulated Slug expression and enhanced the invasion, metastasis and proliferation of lung adenocarcinoma cells. Therefore, FBP1 can be used as one of the potential clinical targets through inhibiting glycolysis, cell invasion and proliferation by inhibiting Slug mediated EMT processes.

Retracted: miR-139-5p Inhibits Lung Adenocarcinoma Cell Proliferation, Migration, and Invasion by Targeting MAD2L1.

[This retracts the article DOI: 10.1155/2020/2953598.].

β-ionone Inhibits Epithelial-Mesenchymal Transition (EMT) in Prostate Cancer Cells by Negatively Regulating the Wnt/β-Catenin Pathway.

β-ionone is a terminal cyclic analog of beta-carotenoids widely found in plants. In recent years, accumulating evidence has shown that β-ionone exerts antitumor effects on various malignant tumors. However, limited studies have revealed the role of β-ionone in regulating the epithelial-mesenchymal transition (EMT) of prostate cancer (PCa) cells. This study aimed to investigate the effect of β-ionone on the EMT process of PCa, focusing on Wnt/β-catenin signaling pathway. After exposure to β-ionone, cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the Brdu proliferation assay. The Transwell and wounding healing were used to investigate the migration and invasion abilities of PCa cells. Expression of proteins involved in the EMT process (E-cadherin, N-cadherin, vimentin) and proteins in the Wnt/β-catenin pathway (β-catenin, GSK3-β, and p-GSK3-β) were explored by western blotting. The effects of β-ionone on β-catenin degradation were explored by cycloheximide tracking assay and in vitro ubiquitination assay. Nude mouse xenograft model was served as the model system in vivo. The migration, invasion, and EMT process of PCa Human PC-3 prostate adenocarcinoma cells (PC3) and Human 22RV1 prostate adenocarcinoma cells (22RV1) cells were significantly inhibited after β-ionone treatment. In addition, β-ionone also inhibited the growth and EMT process of subcutaneous xenograft tumors in nude mice. The study also found that β-catenin, which promotes EMT, was downregulated after β-ionone treatment. Further mechanistic studies revealed that β-ionone inhibited the Wnt/β-catenin pathway by accelerating the ubiquitination and degradation of β-catenin in PCa, thus inhibiting the downstream migration, invasion, and EMT processes. These findings demonstrate that β-ionone may be a potential natural compound targeting the Wnt/β-catenin pathway for the treatment of PCa.

LncRNA LINC02535 Induces Colorectal Adenocarcinoma Progression via Modulating miR-30d-5p/CHD1.

Growing evidence has suggested that lncRNAs play a significant role in the development of colorectal adenocarcinoma. LncRNA LINC02535 was a potential novel lncRNA marker of neoplastic processes of the colon. Nevertheless, the function and mechanisms of LINC02535 in colorectal adenocarcinoma remain unclear. Proteins levels were measured by western blotting. EdU, CCK-8, Transwell, and wound healing assays were performed to investigate the function of LINC02535 in colorectal adenocarcinoma. The distribution of LINC02535 in cells was evaluated by subcellular fractionation assay. The interaction among RNAs was identified by luciferase reporter and RIP assays. In this study, our findings revealed that LINC02535 was highly expressed in colorectal adenocarcinoma cells. Knockdown of LINC02535 inhibited colorectal adenocarcinoma cell proliferation, migration, and invasion. Mechanistically, LINC02535 bound with miR-30d-5p and worked as a competing endogenous RNA to facilitate the expression of messenger RNA chromodomain helicase DNA-binding protein 1 (CHD1). miR-30d-5p directly targeted the sequence of CHD1 3'-untranslated region. Notably, CHD1 upregulation abolished the suppressive influence of LINC02535 inhibition on the malignant phenotypes of colorectal adenocarcinoma cells. Overall, it was disclosed that LINC02535 played an oncogenic role in colorectal adenocarcinoma progression by sponging miR-30d-5p to upregulate CHD1 expression.