Cell Invasion Process Research Articles

Flavopereirine Suppresses the Progression of Human Oral Cancer by Inhibiting the JAK-STAT Signaling Pathway via Targeting LASP1

ObjectiveFlavopereirine has been identified to be a potential anti-cancer agent in several types of human cancer. This study aimed to investigate the anti-cancer activity of flavopereirine in oral cancer.MethodsThe effect of flavopereirine on cell viability of human oral cancer cell lines (BcaCD885 and Tca8113) was evaluated by MTT assay and colony formation assay. Cell apoptosis and cell cycle distribution were detected by flow cytometry. Cell invasion and migration were evaluated by Transwell assay. The expression of LASP1, JAK2, p-JAK2, STST3, p-STST3, STST5 and p-STST5 was evaluated by qRT-PCR and Western blot. In addition, the xenograft mouse model was constructed to determine the anti-cancer role of flavopereirine in vivo.ResultsFlavopereirine significantly inhibited cell proliferation, invasion, migration and EMT process of BcaCD885 and Tca8113 cells, while promoted cell apoptosis in vitro. Flavopereirine markedly decreased the expression levels of p-JAK2, p-STST3 and p-STST5, while increased the expression levels of LASP1. In addition, downregulation of LASP1 significantly increased the expression levels of p-JAK2, p-STAT3 and p-STAT5 compared with si-NC in BcaCD885 cells. Moreover, flavopereirine was found to decrease tumor weight and volume of xenograft tumors in vivo.ConclusionFlavopereirine inhibited the progression of oral cancer through inactivating the JAK/STAT signaling pathway by upregulating LASP1, suggesting that flavopereirine might be a potential anti-cancer agent for oral cancer.

Recent Advances of Small Molecule Focal Adhesion Kinase (FAK) Inhibitors as Promising Anticancer Therapeutics.

Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase involved in the process of cell proliferation, survival, migration, and invasion. It has become a promising therapeutic target for the treatment of human metastatic cancers due to its overexpression and/or activation in multiple cancer types. Since FAK is emerging as a potential cancer target because of its overexpression at both the transcriptional and translational level in cancer, different types of FAK inhibitors with diversified scaffolds have been discovered in the past few years. In this review, the progress of recently discovered small molecule FAK inhibitors was summarized. Major efforts have been focused on the rational design and synthesis of small molecule FAK inhibitors, and their structure-activity relationship (SAR) analysis wasalso discussed. Among them, while type I inhibitors remain as the major focuses, type II inhibitors and novel allosteric FAK inhibitors (type III inhibitors) have been developed to improve both potency and selectivity. Meanwhile, novel strategies, such as targeting FAK using inhibitors of protein-protein interactions, were also discovered. Lastly, some insights and perspectives on the future development of FAK inhibitors as anticancer therapeutics have been provided.

In situ continuously monitoring of cancer cell invasion process based on impedance sensing

Activation of invasion and metastasis is recognized as one of the hallmarks of cancer. There are 90% of cancer-related deaths due to metastasis and given that it is worthy of note to study cancer progression and metastasis. Owing to restricted tools used to underpin the study of tumor invasion process, an on-site platform was developed to monitor this event in vitro. We used interdigital gold electrodes to monitor the dynamic process of cancer cells invading into extracellular matrix in situ continuously. Influences of collagen concentration and number of cancer cells on the measured impedance was exhibited. In addition, the parameters used to demonstrate the experiment results were optimized. The change of impedance magnitude indicated the cell-matrix interaction during invasion process. The potential further use of this platform would be complementary in cell studies when concerning metastasis.

Ferlins and TgDOC2 in Toxoplasma Microneme, Rhoptry and Dense Granule Secretion.

The host cell invasion process of apicomplexan parasites like Toxoplasma gondii is facilitated by sequential exocytosis of the microneme, rhoptry and dense granule organelles. Exocytosis is facilitated by a double C2 domain (DOC2) protein family. This class of C2 domains is derived from an ancestral calcium (Ca2+) binding archetype, although this feature is optional in extant C2 domains. DOC2 domains provide combinatorial power to the C2 domain, which is further enhanced in ferlins that harbor 5–7 C2 domains. Ca2+ conditionally engages the C2 domain with lipids, membranes, and/or proteins to facilitating vesicular trafficking and membrane fusion. The widely conserved T. gondii ferlins 1 (FER1) and 2 (FER2) are responsible for microneme and rhoptry exocytosis, respectively, whereas an unconventional TgDOC2 is essential for microneme exocytosis. The general role of ferlins in endolysosmal pathways is consistent with the repurposed apicomplexan endosomal pathways in lineage specific secretory organelles. Ferlins can facilitate membrane fusion without SNAREs, again pertinent to the Apicomplexa. How temporal raises in Ca2+ combined with spatiotemporally available membrane lipids and post-translational modifications mesh to facilitate sequential exocytosis events is discussed. In addition, new data on cross-talk between secretion events together with the identification of a new microneme protein, MIC21, is presented.

MiR-338-3p inhibits cell growth, invasion, and EMT process in neuroblastoma through targeting MMP-2.

This study aimed to explore the regulatory mechanisms of miR-338-3p and matrix metalloproteinase-2 (MMP-2) in neuroblastoma. Putative target interaction regions of miR-338-3p on MMP-2 were predicted by miRcode and miRbase bioinformatics tools. Relative expression of miRNA-338-3p and MMP-2 in neuroblastoma tissues and GI-LI-N and SK-N-SH cells was determined by reverse transcription polymerase chain reaction experiment. Furthermore, the cell proliferation was determined by Cell Counting Kit-8 assay, the cell apoptosis rate was analyzed by flow cytometry assay, and the cell invasion was evaluated by transwell assay. miR-338-3p expression was downregulated, whereas MMP-2 expression was upregulated in metastasis tissue site compared to that in primary tissue site in total. Furthermore, miR-338-3p overexpression suppressed proliferation, invasion, and epithelial–mesenchymal transition (EMT) of neuroblastoma cells but promoted apoptosis, and the knockdown of MMP-2 triggered similar effects. Furthermore, MMP-2 was directly targeted by miR-338-3p, and overexpression of MMP-2 rescued the inhibitory effects of miR-338-3p on human neuroblastoma cell progression. Collectively, these data demonstrated that miR-338-3p could suppress cell growth, invasion, and EMT pathway and induce apoptosis in neuroblastoma cells by targeting MMP-2. MiR-338-3p sponged MMP-2 to regulate the PI3K/AKT pathway in human neuroblastoma cells.

MicroRNA-4429 restrains colorectal cancer cell invasion and migration via regulating SMAD3-induced epithelial-mesenchymal transition.

Colorectal cancer (CRC) is one of the commonest human cancers and the fourth primary cause of cancer-related death. Previous studies have reported that miR-4429 develops anticancer function in follicular thyroid carcinoma and non-small cell lung cancer. However, whether miR-4429 is implicated in the CRC progression remains to be clarified. The aim of our current study was to explore the potential role of miR-4429 in CRC. According to the result of quantitative real-time polymerase chain reaction analysis, miR-4429 was expressed at a low level in CRC cells. Gain-of-function assays showed that the upregulation of miR-4429 inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) process in CRC, whereas miR-4429 inhibition led to the opposite results. It was uncovered from mechanism experiments that miR-4429 targeted forkhead box M1 (FOXM1) and therefore regulating SMAD family member 3 (SMAD3) expression. Rescue experiments elucidated that miR-4429 influenced cell proliferation, migration, invasion, and EMT process in CRC by targeting FOXM1 to inactivate SMAD3. In conclusion, our study revealed that miR-4429 targeted FOXM1 to decrease SMAD3 expression and thus impeding cell proliferation, migration, invasion, and EMT process of CRC cells.

Zfx-induced upregulation of UBE2J1 facilitates endometrial cancer progression via PI3K/AKT pathway

ABSTRACT Emerging documents revealed that E2 enzyme family has been implicated in regulating the progression of numerous human cancers. Ubiquitin-conjugating enzyme E2 J1 (UBE2J1), a member of E2 enzyme family, has been reported to participate in the biological process of medulloblastoma, while little is known about its functionality in endometrial cancer (EC). Gene expression at the mRNA and protein levels were identified using RT-qPCR and western blot analysis, separately. The alteration on cell proliferation, adhesion, migration, invasion, and epithelial-mesenchymal transition (EMT) process was determined through 5-Ethynyl-2ʹ-deoxyuridine, cell adhesion, wound healing and transwell assays as well as western blot analysis. The role of UBE2J1 in xenograft tumor in mice was determined. Luciferase reporter and chromatin immunoprecipitation assays were conducted to reveal the undering mechanism of UBE2J1. Our results indicated that UBE2J1 displayed high level in EC tissues and cells and predicted poor prognosis of EC patients. In addition, UBE2J1 depletion inhibited cell proliferation, adhesion, motion, EMT process in vitro, and repressed tumor growth in vivo. Rescue assays manifested that ethyl 2-amino-6-chloro-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate treatment reversed the effects of UBE2J1 on PI3K/AKT pathway activation and malignant phenotypes of EC cells. Finally, zinc finger X-chromosomal protein (zfx), with high expression in EC tissues, was verified to activate UBE2J1 transcription by binding to UBE2J1 promoter. In conclusion, all facts signified that zfx-induced upregulation of UBE2J1 accelerated the progression of EC via regulating the PI3K/AKT signaling pathway, which suggested that UBE2J1 might be of great significance in probing into the underlying therapeutic strategies of EC.

Neuron specific enolase promotes tumor metastasis by activating the Wnt/β-catenin pathway in small cell lung cancer

Neuron-specific enolase (NSE) has been used as a specific biomarker for small cell lung cancer (SCLC) patients. Nevertheless, the biological function and mechanism of NSE in SCLC are still unclear. In this study, we clarified the role of NSE in the progression of SCLC and found that NSE expression was positively correlated with distant metastasis. Functional analysis showed that overexpression of NSE promoted migration and invasion of SCLC cells. Mechanism analysis showed that NSE overexpression induced epithelial-mesenchymal transition (EMT) of SCLC cells. Moreover, overexpression of NSE increased the protein expression of β-catenin and its downstream target genes, and silencing β-catenin eliminated NSE-mediated cell migration, invasion and EMT process. Furthermore, NSE interacted with β-catenin and inhibited the degradation of β-catenin. Besides, the animal experiments also indicated that NSE could promote the EMT process and distant metastasis of SCLC cells in vivo. In summary, our results revealed that NSE could promote the EMT process of SCLC cells by activating the Wnt/β-catenin signaling pathway, thereby promoting cell migration, invasion and distant metastasis, which might serve as a potential target for the therapy of SCLC patients.

Proteínas importantes para la invasión de Babesia bovis a las células huésped

Introducción. La babesiosis bovina es causada por parásitos Apicomplexa del género Babesia, siendo Babesia bovis la especie asociada con cuadros clínicos más graves de la enfermedad. La invasión de B. bovis a los eritrocitos bovinos implica la interacción entre moléculas de los merozoítos del parásito con receptores de las células huésped. Por ende, conocer las proteínas involucradas en este proceso supone un importante paso para entender la biología del parásito. Objetivo. Describir las principales moléculas implicadas en el proceso de invasión de B. bovis a eritrocitos bovinos. Metodología. Se realizó una búsqueda en NCBI, Medline, LILACS y SciELO usando los términos: “Babesia bovis AND invasion process”, “MSA-1”, “RON2”, “AMA-1”, “moving junction”, “B. bovis AND Vaccine candidates”. 61 publicaciones disponibles en inglés que describen el estudio de las anteriores proteínas y su participación en la invasión los cuales han sido publicados hasta mayo 2020 se revisaron completamente. Resultados: Siendo el proceso de invasión a eritrocitos bovinos clave para la patogénesis de la babesiosis bovina, se hizo una revisión donde se encontraron 3 proteínas de B. bovis que participan en el reconocimiento e invasión a las células diana: MSA-1, AMA-1 y RON2. Sin embargo, los detalles a nivel molecular para las interacciones inter e intramoleculares aún no se han dilucidado por completo. Conclusiones. Conocer las moléculas involucradas en las interacciones parásito-hospedero permitirá comprender cómo ocurre el proceso de invasión de B. bovis a los eritrocitos y así evaluar su futura utilidad como componente de una estrategia de control efectiva contra esta parasitosis.

MicroRNA-126 suppresses the invasion of trophoblast-model JEG-3 cells by targeting LIN28A

Inadequate trophoblast invasion and impaired trophoblast-induced vascular remodeling are features of preeclampsia. In this context, an angiogenesis-related microRNA, miR-126, is abnormally expressed in preeclampsia placentas, but its role in trophoblast development remains unclear. The purpose of this study was to investigate the roles of miR-126 in the proliferation, migration, and invasion processes of trophoblast cells using the human choriocarcinoma-derived JEG-3 cell line as a model. The mRNA expression profiling of JEG-3 cells with and without miR-126 overexpression, in combination with bioinformatics analysis, identified LIN28A as a putative target of miR-126. The results of real-time RT-PCR and luciferase assay were consistent with this idea. Overexpression of miR-126 in JEG-3 cells decreased the invasive ability of the cells without affecting proliferation or migration. The invasiveness of JEG-3 cells was significantly reduced to a similar extent by knockdown of LIN28A with siRNA and by miR-126-overexpression-induced downregulation of LIN28A, although the level of LIN28A protein was much lower in the siLIN28A-transfected cells. These results indicate that miR-126 suppresses JEG-3 cell invasion by targeting LIN28A, and suggest that miR-126-mediated downregulation of LIN28A might contribute to the onset/deterioration of preeclampsia.

LncRNA MCTP1-AS1 Regulates EMT Process in Endometrial Cancer by Targeting the miR-650/SMAD7 Axis.

BackgroundLong noncoding RNAs (lncRNAs) play critical roles in the pathogenesis of several diseases, especially some kinds of cancer. This study aimed to investigate the expression of MTCP1-AS1 and its effects on endometrial cancer (EC).MethodsMTCP1-AS1 expression level was determined in human EC tissues and cell lines by qRT-PCR. The role of MTCP1-AS1 on EC cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT) was detected by CCK8, wound-healing assay, transwell assay and Western blot, respectively. Moreover, luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) assay were performed to verify the targeting relationship between miR-650, MCTP1-AS1 and SMAD7 in EC cells.ResultsOur data showed that MCTP1-AS1 expression was downregulated in EC tissues and cell lines. Overexpression of MCTP1-AS1 inhibited cell proliferation, migration, invasion and EMT process of EC cells. Moreover, MCTP1-AS1 was proved to be the target of miR-650 and reversely correlated with its expression. In addition, MCTP1-AS1 reversed the effect of miR-650 on the EC cells, which might be associated with the role of SMAD7. Moreover, Western blot showed siRNA-SMAD7 transfection could rescue the repressed TGF-β/SMAD pathway induced by MCTP1-AS1 in EC cells.ConclusionTaken together, these data suggested that lncRNA MCTP1-AS1 inhibited cell proliferation, migration, invasion and EMT process of EC cells via targeting the miR-650/SMAD7 axis and it has the potential to be explored as a therapeutic target for the treatment of EC in the future.

MiR-9-5p promotes cell proliferation and migration of hepatocellular carcinoma by targeting CPEB3.

Objective: This study aimed to observe the effect of miR-9-5p and CPEB3on hepatocellular carcinoma (HCC) cells, and investigate the underlying targeting regulatory mechanism. Materials & methods: Various experiments like CCK-8, colony formation assay, wound healing assay and Transwell were performed for cancer cell activities detection, including cell proliferation, growth activity, migration and invasion. Results: MiR-9-5p was found to be highly expressed in HCC cells, while CPEB3 was poorly expressed (p < 0.05). The overexpression of miR-9-5p and the silencing of CPEB3 both could significantly promote cell proliferation, migration and invasion (p < 0.05). In addition, miR-9-5p could target to downregulate CPEB3 expression, thus accelerating cell proliferation, migration, invasion and epithelial-mesenchymal transition process in HCC. Conclusion: MiR-9-5p can target CPEB3, thereby promoting cell proliferation, migration and invasion in HCC. The axis of miR-9-5p/CPEB3 is expected to become a potential therapeutic target beneficial for HCC patients.

Pseudogene Annexin A2 Pseudogene 1 Contributes to Hepatocellular Carcinoma Progression by Modulating Its Parental Gene ANXA2 via miRNA-376a-3p.

Pseudogenes are defined as key regulators in cancer initiation and progression. But their biological function and clinical significance in hepatocellular carcinoma (HCC) remain to be elucidated. In the current study, we identified a novel pseudogene, Annexin A2 pseudogene 1 (ANXA2P1), in HCC and explored its underlining molecular mechanism. We analyzed the expression pattern of ANXA2P1 in a TCGA dataset and an HCC sample cohort and evaluated its clinical significance. The biological effects on HCC cells proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process were assessed by Cell Counting Kit-8 assay, Transwell assay and Western blot, respectively. The ANXA2P1/miR-376a-3p/ANXA2 axis was determined by bioinformatics analysis and dual-luciferase reporter assays. ANXA2P1 exerted as an oncogene that was significantly overexpressed in HCC tissues and was associated with disease progression and unfavorable prognosis of HCC patients. ANXA2P1 knockdown suppressed cell growth, cell migration and invasion and reversed EMT phenotype in HCC. Mechanistically, ANXA2P1 acts as a competing endogenous RNA for miR-376a-3p, thereby leading to the upregulation of its cognate gene ANXA2. ANXA2P1/miR-376a-3p/ANXA2 axis plays an important role in the progression of HCC. Our findings may provide valuable therapeutic target for treating HCC.

LncRNA SNHG3 Promotes Proliferation and Metastasis of Non-Small-Cell Lung Cancer Cells Through miR-515-5p/SUMO2 Axis.

Lung cancer is a global disease and a major cause of cancer-related mortality worldwide. Accumulated studies have confirmed the essential role of long non-coding RNAs (lncRNAs) in the occurrence and development of cancers. Meanwhile, there have been reports concerning the role of Small Nucleolar RNA Host Gene 3 (SNHG3) in various cancers. However, there are so far few studies on the function and mechanism of SNHG3 in lung cancer. In the present study, SNHG3 was found to be highly expressed in lung cancer tissues and cells. Downregulation of SNHG3 could inhibit cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process. In addition, SNHG3 was found to have the ability to bind to miR-515-5p. Furthermore, Small Ubiquitin Like Modifier 2 (SUMO2) was identified to be the downstream target of miR-515-5p, which was negatively correlated with miR-515-5p expression. SNHG3 could positively regulate SUMO2 expression by sponging miR-515-5p. In addition, the rescue experiment showed that simultaneous transfection of miR-515-5p or SUMO2 siRNA could reverse the effect of SNHG3 expression on cell proliferation and metastasis. Collectively, our study demonstrates that SNHG3 can act on miR-515-5p in the form of competitive endogenous RNA (ceRNA) to regulate SUMO2 positively and thus affect the proliferation and metastasis of NSCLC cells. Findings in our study support that SNHG3/miR-515-5p/SUMO2 regulatory axis may become a potential therapeutic target for lung cancer.

Overexpression of FBXO17 Promotes the Proliferation, Migration and Invasion of Glioma Cells Through the Akt/GSK-3β/Snail Pathway

FBXO17 is a newly studied F-box protein associated with high-grade glioma. However, its exact role in glioma remains unclear. In the present study, we aimed to investigate the role of FBXO17 in glioma both in vitro and in vivo and explore the underlying mechanism. Our results showed that FBXO17 mRNA and protein levels were upregulated in glioma cells including U87, U251, SHG44, and U-118-MG cells as compared to the HA1800 cells. Downregulation of FBXO17 significantly suppressed the cellular behaviors of glioma cells including cell proliferation, migration, and invasion. In addition, FBXO17 knockdown induced E-cadherin expression and inhibited N-cadherin and vimentin expression at mRNA and protein levels in glioma cells. In contrast, overexpression of FBXO17 promoted cell proliferation, migration, invasion and EMT process. Furthermore, FBXO17 regulated the Akt/GSK-3β/snail signaling pathway in glioma cells with significant changes in the expression levels of p-Akt, p-GSK-3β and snail. Additionally, inhibition of Akt by LY294002 reversed the effects of FBXO17 overexpression on cellular behaviors of glioma cells. Finally, in vivo mouse xenograft assay proved that downregulation of FBXO17 suppresses the tumorigenesis of glioma. In conclusion, these findings demonstrated that FBXO17 acted as a promotor of glioma development via modulating Akt/GSK-3β/snail signaling pathway.

LncRNA RAD51-AS1/miR-29b/c-3p/NDRG2 crosstalk repressed proliferation, invasion and glycolysis of colorectal cancer.

LncRNAs are recently increasingly emerging as molecules that take its part in human carcinogenesis. A large body of literature has identified the functional roles of lncRNAs in the pathophysiology of CRC. The current study was intended to provide new ideas and perspectives for the functional role of lncRNA RAD51-AS1 in regulating CRC progression. Herein, a survey of RAD51-AS1 expression profile in The Cancer Genome Atlas (TCGA)-colon adenocarcinoma (COAD) dataset revealed that RAD51-AS1 was downregulated in COAD specimens. Consistently, RAD51-AS1 expression was observed to be lower in CRC cell lines compared with normal cell line (NCM460). In the meanwhile, both the levels of miR-29b-3p and miR-29c-3p were prominently elevated in CRC cells. Functionally, administration of RAD51-AS1 refrained growth, invasion and migration of CRC cells. Additionally, accumulation of RAD51-AS1 hampered glucose consumption and lactate production, as well as the restraint of hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) levels. More important, RAD51-AS1 functioned as a competing endogenous RNA (ceRNA) for sponging miR-29b-3p and miR-29c-3p, leading to enhancement of their common target N-myc downstream-regulated gene 2 (NDRG2). Mechanistically, the delivery of miR-29b/c-3p mimics or ablation of NDRG2 effectively blunted the salutary effects of RAD51-AS1 on CRC cell behaviors. Moreover, augmentation of RAD51-AS1 inhibited the tumorigenesis of CRC cells in vivo. Collectively, these findings provide comprehensive evidence that RAD51-AS1 repressed cell proliferation, migration, invasion and glycolysis process, ultimately contributing to the progression of CRC by repressing the miR-29b/c-3p/NDRG2 signaling axis, insinuating the putative potential of RAD51-AS1/miR-29b/c-3p/NDRG2 interaction network in unraveling CRC pathology and hopefully contributed to the treatment of CRC patients.

Review on Mathematical Approaches of Cancer Cell Invasion at Subcellular Level

Metastasis is a process of cancer cell invasion which is the main cause of death among cancer patients. Invasion of a cancer cell on tissue compartment is initiated by the formation of protrusions known as invadopodia and the degradation of extracellular membrane (ECM) barrier. Invadopodia is one of the subcellular viewson a cancer cell formed by several processes including ligand formation, signal transduction,chemotaxis, matrix metalloproteinases (MMPs) up regulation and degradation of ECM proteins. Mathematical approach of the cancer cell invasion based on the hypothesis and illustration of previous studies has been considered in order to understand the vivo dynamics of invasion. This study had been done progressively at tissue and cellular levels in the past decades. Recently, mathematical modelling on the study of cancer cell invasion at subcellular level have received much attention since there is potential on anti-invasion therapies for treating the cancer patients. Here, the reviews of mathematical models on cancer cell invasion at subcellular level are able to extend our knowledge on the fields of mathematical medicine and biology.

Cytoskeletal Remodeling in Cancer.

Simple SummaryCell migration is an essential process from embryogenesis to cell death. This is tightly regulated by numerous proteins that help in proper functioning of the cell. In diseases like cancer, this process is deregulated and helps in the dissemination of tumor cells from the primary site to secondary sites initiating the process of metastasis. For metastasis to be efficient, cytoskeletal components like actin, myosin, and intermediate filaments and their associated proteins should co-ordinate in an orderly fashion leading to the formation of many cellular protrusions-like lamellipodia and filopodia and invadopodia. Knowledge of this process is the key to control metastasis of cancer cells that leads to death in 90% of the patients. The focus of this review is giving an overall understanding of these process, concentrating on the changes in protein association and regulation and how the tumor cells use it to their advantage. Since the expression of cytoskeletal proteins can be directly related to the degree of malignancy, knowledge about these proteins will provide powerful tools to improve both cancer prognosis and treatment.Successful metastasis depends on cell invasion, migration, host immune escape, extravasation, and angiogenesis. The process of cell invasion and migration relies on the dynamic changes taking place in the cytoskeletal components; actin, tubulin and intermediate filaments. This is possible due to the plasticity of the cytoskeleton and coordinated action of all the three, is crucial for the process of metastasis from the primary site. Changes in cellular architecture by internal clues will affect the cell functions leading to the formation of different protrusions like lamellipodia, filopodia, and invadopodia that help in cell migration eventually leading to metastasis, which is life threatening than the formation of neoplasms. Understanding the signaling mechanisms involved, will give a better insight of the changes during metastasis, which will eventually help targeting proteins for treatment resulting in reduced mortality and longer survival.

LINC00861 inhibits the progression of cervical cancer&nbsp;cells by functioning as a ceRNA for miR‑513b‑5p and&nbsp;regulating the PTEN/AKT/mTOR signaling pathway.

Long non-coding RNAs (lncRNAs) have been discovered to serve important roles in a variety of types of cancer, including cervical cancer. The low expression of lncRNA long intergenic non-protein coding RNA 861 (LINC00861) is related to poor prognosis in ovarian cancer. However, the effects and underlying mechanisms of LINC00861 in cervical cancer remain largely unknown. The present study aimed to examine the role of LINC00861 in the development and progression of ovarian cancer and its underlying mechanisms. The expression levels of LINC00861 and microRNA (miR)-513b-5p were analyzed using reverse transcription-quantitative PCR analysis. Cell proliferation, migration and invasion were measured by using Cell Counting Kit-8, colony formation, wound healing and Transwell assays, respectively. A luciferase assay was used to determine whether miR-513b-5p targeted LINC00861 and PTEN. The expression of protein was measured by using western blot assay. The results of the present study discovered that LINC00861 expression levels were significantly downregulated in cervical cancer tissues and CaSki and ME-180 cell lines. Downregulated LINC00861 expression levels were identified to be associated with an advanced-stage, lymph node metastasis and the poor survival of patients with cervical cancer. Gene Set Enrichment Analysis revealed that the PI3K/AKT/mTOR signaling pathway was significantly enriched in cervical tumors expressing low expression levels of LINC00861 compared with tumors expressing high levels of LINC00861. The overexpression of LINC00861 reduced cervical cancer cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) processes, upregulated PTEN protein expression levels and downregulated phosphorylated (p)-AKT and p-mTOR protein expression levels. The regulatory relationship between LINC00861, microRNA (miR)-513b-5p and PTEN was validated using a dual luciferase reporter gene assay. PTEN expression levels were significantly downregulated in the miR-513b-5p mimic group and significantly upregulated in the miR-513b-5p inhibitor group compared with the mimic NC and inhibitor NC in both cell lines. Furthermore, LINC00861 was suggested to serve as a competing endogenous RNA by sponging miR-513b-5p and consequently upregulating the expression levels of PTEN in cervical cancer cells. The expression of PTEN, the phosphorylation of Akt and mTOR and and the EMT phenotype were rescued following co-transfection with LINC00861 and miR-513b-5p mimics. In conclusion, the findings of the present study indicated that the LINC00861/miR-513b-5p axis may inhibit the progression of cervical cancer cells through the PTEN/AKT/mTOR signaling pathway to suppress the EMT process.

Serum LUCAT1 implicates the pathogenesis of muscle-invasive bladder cancer via targeting miR-199a-5p and miR-199b-5p.

Muscle-invasive bladder cancer (MIBC) is a common malignancy of urinary system cancers, accounting for about 1/3 of all newly diagnosed bladder cancer cases. Due to its strong metastasis, the 5-year survival of MIBC is less than 50%, and in serious cases, the overall survival of metastatic bladder cancer patients is about 1.3years. LncRNAs, a type of non-coding RNAs defined as the transcripts exceeding 200 nucleotides in length, are frequently aberrant in multiple cancers including cervical, ovarian, breast and bladder cancers. Recently, LUCAT1 (short for lung cancer-associated transcript 1), a lncRNA first reported to be involved in smoking-related lung cancer, has been observed to exhibit crucial roles in the epithelial-to-mesenchymal transition (EMT), migration and invasion processes of clear cell renal cell carcinoma (ccRCC) and colorectal cancer. However, whether it involves in the pathogenesis of MIBC remains underexplored. In the present study, LUCAT1 was up-regulated in the serum samples of MIBC patients and bladder cancer cell lines, as assessed using real-time PCR. Our in vitro data (including wound healing and trans-well assays) showed that LUCAT1 was required for the proliferation, EMT, migration and invasion processes of T24 cells. Moreover, LUCAT1 directly targeted miR-199a-5p and miR-199b-5p, as affirmed using the luciferase reporter assay, and manipulation of LUCAT1 significantly suppressed miR-199a-5p and miR-199b-5p. Collectively, our findings highlight an axis of LUCAT1/miR-199a/b-5p in MIBC pathogenesis. Therefore, LUCAT1 may possibly be a promising candidate for diagnostic biomarker and therapeutic target of MIBC.