Regulates Cancer Cell Behavior Research Articles

Establishment of disulfidptosis-related LncRNA signature as biomarkers in colon adenocarcinoma.

Metabolic reprogramming is a hallmark of cancer and plays a key role in precision oncology treatment. Long non-coding RNAs (lncRNAs) regulate cancer cell behavior, including metabolism. Disulfidptosis, a newly identified form of regulated cell death triggered by glucose starvation, has yet to be fully understood in colon adenocarcinoma (COAD). This study aimed to confirm the existence and role of disulfidptosis in COAD and identify disulfidptosis-related lncRNAs that may be targeted to induce disulfidptosis in COAD. PI and F-actin staining were used to observe disulfidptosis in COAD cell lines. Disulfidptosis-related lncRNAs were identified based on the expression of disulfidptosis-associated genes in the TCGA-COAD database. A four-lncRNA signature for disulfidptosis was established. Subsequently, loss-of-function assays explored the roles of AC013652.1 and MCM3AP-AS1 in disulfidptosis. Disulfidptosis was observed in COAD cells under glucose starvation and could be reversed by agents that prevent disulfide stress, such as dithiothreitol (DTT) and tris-(2-carboxyethyl)-phosphine (TCEP). The prognostic value of disulfidptosis-associated genes in COAD patients was confirmed, with higher expression indicating longer survival. A disulfidptosis-related lncRNA signature comprising four lncRNAs was established based on the expression of these genes. Among these, AC013652.1 and MCM3AP-AS1 predicted worse prognoses. Furthermore, inhibiting AC013652.1 or MCM3AP-AS1 increased disulfidptosis-associated gene expression and cellular death, which could be reversed by DTT and TCEP. This study provides hitherto undocumented evidence of the existence of disulfidptosis and the prognostic value of disulfidptosis-associated genes in COAD. Importantly, we identified lncRNAs AC013652.1 and MCM3AP-AS1, which suppress disulfidptosis and may serve as potential therapeutic targets for COAD.

MKLN1-AS promotes pancreatic cancer progression as a crucial downstream mediator of HIF-1α through miR-185-5p/TEAD1 pathway

In pancreatic ductal adenocarcinomas (PDAC), profound hypoxia plays key roles in regulating cancer cell behavior, including proliferation, migration, and resistance to therapies. The initial part of this research highlights the important role played by long noncoding RNA (lncRNA) MKLN1-AS, which is controlled by hypoxia-inducible factor-1 alpha (HIF-1α), in the progression of PDAC. Human samples of PDAC showed a notable increase in MKLN1-AS expression, which was linked to a worse outcome. Forced expression of MKLN1-AS greatly reduced the inhibitory impact on the growth and spread of PDAC cells caused by HIF-1α depletion. Experiments on mechanisms showed that HIF-1α influences the expression of MKLN1-AS by directly attaching to a hypoxia response element in the promoter region of MKLN1-AS.MKLN1-AS acts as a competitive endogenous RNA (ceRNA) by binding to miR-185-5p, resulting in the regulation of TEAD1 expression and promoting cell proliferation, migration, and tumor growth. TEAD1 subsequently enhances the development of PDAC. Our study results suggest that MKLN1-AS could serve as a promising target for treatment and a valuable indicator for predicting outcomes in PDAC. PDAC is associated with low oxygen levels, and the long non-coding RNA MKLN1-AS interacts with TEAD1 in this context.Graphical abstract

Abstract 4582: HDAC6 inhibition reshapes the epigenome of cancer via P300 stabilization

Abstract Introduction: Histone deacetylases (HDACs)are crucial in regulating gene expression, DNA synthesis, and metabolic processes, including cancer, in various cellular environments. The unique structural and functional attributes of class IIb HDAC6 position it as a key player in influencing protein stability and chromatin dynamics. While its role in cancer progression and immunomodulation is well-recognized, the in-depth mechanisms following HDAC6 inactivation, particularly its influence on chromatin remodeling and gene regulation, are not thoroughly understood. This knowledge gap represents a critical area of investigation, given the potential of HDAC6 as a therapeutic target in oncology. This study aims to elucidate HDAC6 inactivation-dependent epigenetic effects of, exploring the possibility to exploit these latter for therapeutic purposes in cancer. This aim includes an examination of the stabilization of the lysine acetyltransferase P300 and its implications for chromatin structure and function. Methods & Results: In this study, ITF3756 and CRISPR/Cas9 were employed to inactivate HDAC6 across a variety of cancer cell lines (Jurkat, MDA 231, HCC1806, 4T1, and B16F10 melanoma). ATAC-seq and H3K27Ac ChIP-seq were used to investigate changes in chromatin accessibility, revealing significant alterations, particularly in introns and distal intergenic regions. Gene Ontology (GO) analysis further supported this alteration in the chromatin landscape, which indicated a differential expression of genes involved in critical cellular processes like cell proliferation, adhesion, migration, and apoptosis. A notable outcome of this study was the stabilization of P300 following ITF3756 treatment, an effect that was paralleled by changes in the expression of critical genes, including AKT1, ITGB3, GAS6, SOX9, NF1, TGFB2, and CASP7. These genes are integral to cellular survival mechanisms, and their modulation emphasizes the role of HDAC6 in cancer cell physiology. Conclusions: This research shows that the chemical or genetic inactivation of HDAC6 impacts cancer cell proliferation and chromatin architecture, underscoring the potential of HDAC6 as a target in cancer therapeutics.. A critical finding of this study is the stabilization of P300, which offers new perspectives on HDAC6's functionality and its role as an epigenetic modifier in cancer cells. This study contributes to the field by suggesting therapeutic strategies focusing on HDAC/HAT pharmacological targeting, thereby advancing our understanding of the role of HDAC6 in regulating cancer cell behavior and epigenetic landscape. Citation Format: Michela Gottardi Zamperla, Barbara Illi, Veronica Barbi, Chiara Cencioni, Stella Gagliardi, Maria Garofalo, Gabriele Antonio Zingale, Irene Pandino, Diego Sbardella, Lina Cipolla, Simone Sabbioneda, Antonella Farsetti, Chiara Ripamonti, Gianluca Fossati, Christian Steinkühler, Sandra Atlante, Carlo Gaetano. HDAC6 inhibition reshapes the epigenome of cancer via P300 stabilization [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4582.

Defining Integrin Tension Required for Chemotaxis of Metastatic Breast Cancer Cells in Confinement.

Cancer metastasis is affected by chemical factors and physical cues. From cell adhesion to migration, mechanical tension applied to integrin expresses on the cell membrane and physical confinement significantly regulates cancer cell behaviors. Despite the physical interplay between integrins in cells and ligands in the tumor microenvironment, quantitative analysis of integrin tension during cancer cell migration in microconfined spaces remains elusive owing to the limited experimental tools. Herein, a platform termed microconfinement tension gauge tether to monitor spatial integrin tension with single-molecule precision by analyzing the epithelial-growth-factor-induced chemotaxis of metastatic human breast cancer cells in microfluidic channels is developed. The results reveal that the metastatic cancer cells exert the strongest integrin tension in the range of 54-100pN at the leading edges of cells during chemokinetic migration on a planar surface, while the cells exert the strongest integrin tension exceeding 100pN at the cell rear when entering microconfinement. Further analysis demonstrates that cells undergo mesenchymal migration under high integrin tension and less confinement, which is converted to amoeboid migration under low integrin tension or high confinement. In summary, the results identify a basic mechanism underlying the mechanical interactions between integrin tension and microenvironment that determines cancer invasion and metastasis.

An updated review of contribution of long noncoding RNA-NEAT1 to the progression of human cancers.

Long non-coding RNAs (lncRNAs) present pivotal roles in cancer tumorigenesis and progression. Recently, nuclear paraspeckle assembly transcript 1 (NEAT1) as a lncRNA has been shown to mediate cell proliferation, migration, and EMT in tumor cells. NEAT1 by targeting several miRNAs/mRNA axes could regulate cancer cell behavior. Therefore, NEAT1 may function as a potent biomarker for the prediction and treatment of some human cancers. In this review, we summarized various NEAT1-related signaling pathways that are critical in cancer initiation and progression.

CD44 Promotes Breast Cancer Metastasis through AKT-Mediated Downregulation of Nuclear FOXA2.

The primary cause of breast cancer mortality is the metastatic invasion of cancerous stem cells (CSC). Cluster of differentiation 44 (CD44) is a well-known CSC marker in various cancers, as well as a key role player in metastasis and relapse of breast cancer. CD44 is a cell-membrane embedded protein, and it interacts with different proteins to regulate cancer cell behavior. Transcription factor forkhead box protein A2 (FOXA2) acts as an important regulator in multiple cancers, including breast cancer. However, the biological significance of CD44-FOXA2 association in breast cancer metastasis remains unclear. Herein, we observed that CD44 expression was higher in metastatic lymph nodes compared to primary tumors using a flow cytometric analysis. CD44 overexpression in breast cancer cell lines significantly promoted cell migration and invasion abilities, whereas the opposite effects occurred upon the knockdown of CD44. The stem cell array analysis revealed that FOXA2 expression was upregulated in CD44 knockdown cells. However, the knockdown of FOXA2 in CD44 knockdown cells reversed the effects on cell migration and invasion. Furthermore, we found that CD44 mediated FOXA2 localization in breast cancer cells through the AKT pathway. Moreover, the immunofluorescence assay demonstrated that AKT inhibitor wortmannin and AKT activator SC79 treatment in breast cancer cells impacted FOXA2 localization. Collectively, this study highlights that CD44 promotes breast cancer metastasis by downregulating nuclear FOXA2.

The interplay between physical cues and mechanosensitive ion channels in cancer metastasis.

Physical cues have emerged as critical influencers of cell function during physiological processes, like development and organogenesis, and throughout pathological abnormalities, including cancer progression and fibrosis. While ion channels have been implicated in maintaining cellular homeostasis, their cell surface localization often places them among the first few molecules to sense external cues. Mechanosensitive ion channels (MICs) are especially important transducers of physical stimuli into biochemical signals. In this review, we describe how physical cues in the tumor microenvironment are sensed by MICs and contribute to cancer metastasis. First, we highlight mechanical perturbations, by both solid and fluid surroundings typically found in the tumor microenvironment and during critical stages of cancer cell dissemination from the primary tumor. Next, we describe how Piezo1/2 and transient receptor potential (TRP) channels respond to these physical cues to regulate cancer cell behavior during different stages of metastasis. We conclude by proposing alternative mechanisms of MIC activation that work in tandem with cytoskeletal components and other ion channels to bestow cells with the capacity to sense, respond and navigate through the surrounding microenvironment. Collectively, this review provides a perspective for devising treatment strategies against cancer by targeting MICs that sense aberrant physical characteristics during metastasis, the most lethal aspect of cancer.

Mechanical properties of breast, kidney, and thyroid tumours measured by AFM: Relationship with tissue structure

The mechanical properties of the extracellular matrix are essential for regulating cancer cell behavior, but how they change depending on tumour type remains unclear. The aim of the current study was to determine how the mechanical properties of tumours that frequently metastasize to bones were affected depending on histological type. Human breast, kidney, and thyroid specimens containing tumour and normal tissue were collected during surgery. The elastic modulus and elastic fraction of each sample were characterized using atomic force microscopy and compared with histopathological markers. We observed that tumour mechanical properties were differentially affected depending on organ and histological type. Indeed, clear cell renal carcinoma and poorly differentiated thyroid carcinoma displayed a decrease in the elastic modulus compared to their normal counterpart, while breast tumours, papillary renal carcinoma and fibrotic thyroid tumours displayed an increase in the elastic modulus. Elastic fraction decreased only for thyroid tumour tissue, indicating an increase in viscosity. These findings suggest a unique mechanical profile associated with each subtype of cancer. Therefore, viscosity could be a discriminator between tumour and normal thyroid tissue, while elasticity could be a discriminator between the subtypes of breast, kidney and thyroid cancers.

Epigenetic and Transcriptional Regulation of Innate Immunity in Cancer.

Innate immune cells participate in the detection of tumor cells via complex signaling pathways mediated by pattern-recognition receptors, such as Toll-like receptors and nucleotide-binding and oligomerization domain-like receptors. These pathways are finely tuned via multiple mechanisms, including epigenetic regulation. It is well established that hematopoietic progenitors generate innate immune cells that can regulate cancer cell behavior, and the disruption of normal hematopoiesis in pathologic states may lead to altered immunity and the development of cancer. In this review, we discuss the epigenetic and transcriptional mechanisms that underlie the initiation and amplification of innate immune signaling in cancer. We also discuss new targeting possibilities for cancer control that exploit innate immune cells and signaling molecules, potentially heralding the next generation of immunotherapy.

Hyaluronan as "Agent Smith" in cancer extracellular matrix pathobiology: Regulatory roles in immune response, cancer progression and targeting.

Extracellular matrix (ECM) critically regulates cancer cell behavior by governing cell signaling and properties. Hyaluronan (HA) acts as a structural and functional ECM component that mediates critical properties of cancer cells in a molecular size-dependent manner. HA fragments secreted by cancer-associated fibroblasts (CAFs) reveal the correlation of HA to CAF-mediated matrix remodeling, a key step for the initiation of metastasis. The main goal of this article is to highlight the vital functions of HA in cancer cell initiation and progression as well as HA-mediated paracrine interactions among cancer and stromal cells. Furthermore, the HA implication in mediating immune responses to cancer progression is also discussed. Novel data on the role of HA in the formation of pre-metastatic niche may contribute towards the improvement of current theranostic approaches that benefit cancer management.

Retraction: LncRNA SRA1 is downregulated in HPV-negative cervical squamous cell carcinoma (CSCC) and regulates cancer cell behaviors.

This article is being retracted from Bioscience Reports at the request of the Editorial Board following receipt of a notification from a reader, alerting the Editorial Board to a potential concern with the ethics statement in the article, which had similarities with other published papers and did not match the affiliations of any of the authors.The authors were contacted by the Journal, but did not respond to any correspondence from the Editorial Office. Subsequently, the Editorial Office has been contacted by the authors to state that they were unaware of the submission to the Journal and that the email addresses used were not theirs (despite this correspondence email being the same as that used throughout the article history and as listed in the Version of Record). In this latest correspondence from the authors, they ask that the paper be withdrawn. The Editor-in-Chief and Editorial Board agree with the retraction.

3D printing novel in vitro cancer cell culture model systems for lung cancer stem cell study

Two-dimensional (2D) in vitro cell cultures and laboratory animals have been used traditionally as the gold-standard preclinical cancer model systems. However, for cancer stem cell (CSC) studies, they exhibit notable limitations on simulating native environment, which depreciate their translatability for clinical development purposes. In this study, different three-dimensional (3D) printing platforms were used to establish novel 3D cell cultures enriched in CSCs from non-small cell lung cancer (NSCLC) patients and cell lines. Rigid scaffolds with an elevated compressive modulus and uniform pores and channels were produced using different filaments. Hydrogel-based scaffolds were printed with a more irregular distribution of pores and a lower compressive modulus. As a 3D model of reference, suspension spheroid cultures were established. Therein, cancer cell lines exhibited enhanced proliferation profiles on rigid scaffolds compared to the same cells grown on either hydrogel scaffolds or tumor spheres. Meanwhile, primary cancer cells grew considerably better on hydrogel scaffolds or in tumor sphere culture, compared to cells grown on rigid scaffolds. Gene expression analysis confirmed that tumor spheres and cells seeded on hydrogel scaffolds significantly overexpress most of stemness and invasion promoters tested compared to control cells grown in 2D culture. A different phenomenon was observed within cells growing on the rigid scaffolds, where fewer significant variations in gene expression were detected. Our findings provide strong evidence for the advantageous usage of 3D printed models, especially those which use GelMA-PEGDA hydrogels as the primary scaffold material, for studying lung CSCs. The results demonstrated that the 3D printed scaffolds were better to mimic tumor complexity and regulate cancer cell behavior than in vivo 2D culture models.

Multifaceted activities of transcription factor EB in cancer onset and progression.

Transcription factor EB (TFEB) represents an emerging player in cancer biology. Together with microphthalmia-associated transcription factor, transcription factor E3 and transcription factor EC, TFEB belongs to the microphthalmia family of bHLH-leucine zipper transcription factors that may be implicated in human melanomas, renal and pancreatic cancers. TFEB was originally described as being translocated in a juvenile subset of pediatric renal cell carcinoma; however, whole-genome sequencing reported that somatic mutations were sporadically found in many different cancers. Besides its oncogenic activity, TFEB controls the autophagy-lysosomal pathway by recognizing a recurrent motif present in the promoter regions of a set of genes that participate in lysosome biogenesis; furthermore, its dysregulation was found to have a crucial pathogenic role in different tumors by modulating the autophagy process. Other than regulating cancer cell-autonomous responses, recent findings indicate that TFEB participates in the regulation of cellular functions of the tumor microenvironment. Here, we review the emerging role of TFEB in regulating cancer cell behavior and choreographing tumor-microenvironment interaction. Recognizing TFEB as a hub of network of signals exchanged within the tumor between cancer and stroma cells provides a fresh perspective on the molecular principles of tumor self-organization, promising to reveal numerous new and potentially druggable vulnerabilities.

Engineering the Extracellular Matrix to Model the Evolving Tumor Microenvironment.

SummaryClinical evidence supports a role for the extracellular matrix (ECM) in cancer risk and prognosis across multiple tumor types, and numerous studies have demonstrated that individual ECM components impact key hallmarks of tumor progression (e.g., proliferation, migration, angiogenesis). However, the ECM is a complex network of fibrillar proteins, glycoproteins, and proteoglycans that undergoes dramatic changes in composition and organization during tumor development. In this review, we will highlight how engineering approaches can be used to examine the impact of changes in tissue architecture, ECM composition (i.e., identity and levels of individual ECM components), and cellular- and tissue-level mechanics on tumor progression. In addition, we will discuss recently developed methods to model the ECM that have not yet been applied to the study of cancer.

Abstract 4425: Extracellular matrix segmentation combined with cell classification as a novel method for detailed tumor tissue mapping

Abstract Tumor microenvironment (TME) represents a dynamic niche that regulates cancer cell behavior contributing directly to disease outcome. Systemic approach to analysis of TME should uncover its complexity and facilitate discovery of mechanisms orchestrating tumor development and metastasis. Multiplexed fluorescent tissue stain followed by spatial analysis of tumor tissue architecture can provide insights to pivotal interactions of cellular and acellular components of TME. Extracellular matrix (ECM), one of constitutive of TME, is represented mainly by collagen deposition. Recently it is became increasingly recognized that ECM contribution to TME dynamics not only depend upon amount of accumulated collagen but its geometrical features and spatial orientation of fibers. These characteristics of collagen contribute directly to physical and mechanical properties of tissue and can contribute to tumor growth and metastasis. Current algorithms of tissue stain-based methods include estimation of ECM deposition by measuring percent of positive area and separate to it cell classification and cell count. The goal of current work was to develop a new computational tool to perform spatial distribution analysis based on geometrical features and orientation of collagen fibers in combination with cell class assessment aimed to achieve detailed tumor tissue mapping. To pursue this goal, we generated fluorescent images of human breast tumor tissue, stained for following markers: CD3 - marker of T-lymphocytes, PanCytokeratin - marker of epithelial/tumor cells, collagen hybridizing peptide (3Helix) - marker of collagen, DAPI - nuclear counterstain. To develop image analysis pipeline, we utilized open source graphical interface analytical platform KNIME, where we generated modular workflow. For ECM analysis, we integrated Python written code into KNIME node. Segmentation of collagen fibers was performed using skeletonization with subsequent calculation of geometrical properties (length, alignment, widths) and orientation of each fiber. Data, collected from single cell analysis and ECM architecture assessment, were combined and forwarded to downstream spatial analysis, where distances from cell to cell or cell to ECM were computed and neighborhood analysis was performed. We demonstrate different patterns in tumor microenvironment organization that correlate with cancer outcome. Developed image analysis algorithm provides additional dimensionality to fluorescent tissue stains and can reveal underrecognized patterns of tumor microenvironment that can contribute to better understanding of tumorigenesis and metastasis. Citation Format: GEORGII VASIUKOV, Tatiana Novitskaya, Sergey Gutor, Anna Menshikh, Andries Zijlstra, Sergey Novitskiy. Extracellular matrix segmentation combined with cell classification as a novel method for detailed tumor tissue mapping [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4425.

LINC00324 affects non-small cell lung cancer cell proliferation and invasion through regulation of the miR-139-5p/IGF1R axis.

Long non-coding RNAs (lncRNAs) are proved to perform critical function in regulating cancer cell behavior. It is reported that LINC00324 promotes lung adenocarcinoma development by regulating miR-615-5p/AKT1 axis. This study aimed to demonstrate whether LINC00324 participates in non-small cell lung cancer (NSCLC) pathogenesis through other molecular mechanism. Relative mRNA, lncRNA, and microRNA levels were analyzed using quantitative real-time-polymerase chain reaction (qRT-PCR). Western blot was used to detect protein level. MTT assay shown proliferation ability and transwell assay shown invasive ability. Luciferase reporter assay illustrated the interaction between RNA molecules. In NSCLC, the high expression of LINC00324 had correlation with the poor prognosis. LINC00324 promoted the proliferation and invasion of NSCLC cells while miR-139-5p inhibited these behaviors. LINC00324 overexpression promoted insulin-like growth factor 1 receptor (IGF1R) expression via absorbing miR-139-5p. The tumor-promoting effects of LINC00324 were attenuated through miR-139-5p overexpression. Highly expressed LINC00324 in NSCLC through sponged miR-139-5p to elevate IGF1R expression and promoted cell proliferation and invasion. This research demonstrated that LINC00324 is a potential NSCLC diagnosis and therapy target.

Expression of Concern: LncRNA SRA1 is downregulated in HPV-negative cervical squamous cell carcinoma (CSCC) and regulates cancer cell behaviors.

The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates.

MIR4435-2HG regulates cancer cell behaviors in oral squamous cell carcinoma cell growth by upregulating TGF-β1.

MIR4435-2HG has been characterized as an oncogenic lncRNA in several types of cancer, while its role in oral squamous cell carcinoma (OSCC, a major subtype of oral cancer) has not been characterized. We explored the functionality of MIR4435-2HG in OSCC and investigated its interactions with TGF-β1. Blood samples were extracted from OSCC patients (n = 44) and healthy volunteers (n = 38), RT-qPCR, CCK-8, Transwell assays and western blot were performed in this study. The results showed that levels of MIR4435-2HG and TGF-β1 in plasma were upregulated in OSCC. Across OSCC plasma samples, TGF-β1 and MIR4435-2HG were significantly and positively correlated. Overexpression of MIR4435-2HG resulted in upregulated TGF-β1 expression, while exogenous TGF-β1 treatment had no effect on the expression of MIR4435-2HG. Overexpression of MIR4435-2HG and exogenous TGF-β1 treatment led to promoted, while TGF-β inhibitor led to inhibited migration, proliferation and invasion of cancer cells. Moreover, TGF-β inhibitor led to reduced effects of overexpressing MIR4435-2HG. Therefore, MIR4435-2HG regulates the behaviors of OSCC cells by promoting the expression of TGF-β1.

LncRNA E2F-Mediated Cell Proliferation Enhancing lncRNA Regulates Cancer Cell Behaviors and Affects Prognosis of Gastric Cancer.

A recent study reported a novel long non-coding RNA (lncRNA) E2F-mediated cell proliferation enhancing lncRNA (EPEL, human chromosome 4, intergenic region) plays an oncogenic role in lung cancer. We aimed to investigate the role of lncRNA EPEL in gastric cancer. Gene expression was analyzed by RT-qPCR and western blot. Survival analysis was performed by comparing survival curves. Cell proliferation, migration, and invasion were analyzed by CCK-8 and Transwell assays. We found that lncRNA EPEL and Runt-related transcription factor 2 (RUNX2) were both upregulated in gastric cancer. EPEL and RUNX2 were positively correlated in tumor. Patients with high expression level of lncRNA EPEL showed poor survival. LncRNA EPEL and RUNX2 overexpression promoted, while lncRNA EPEL siRNA silencing inhibited the migration, proliferation, and invasion of gastric cancers. In addition, RUNX2 overexpression completely rescued the inhibited cancer cell migration, proliferation, and invasion caused by lncRNA EPEL siRNA silencing. Consistently, EPEL overexpression resulted in upregulated RUNX2 expression, while RUNX2 overexpression did not affect lncRNA EPEL expression. Therefore, lncRNA EPEL may regulate cancer cell behaviors and affect prognosis of gastric cancer by interacting with RUNX2.

LncRNA SRA1 is down-regulated in HPV-negative cervical squamous cell carcinoma and regulates cancer cell behaviors.

LncRNA SRA1 plays important roles in several types of human diseases. The present study aimed to explore the role of SRA1 in cervical squamous cell carcinoma (CSCC). In the present study, we showed that plasma SRA1 was down-regulated in human papillomavirus (HPV)-negative CSCC patients but not in HPV-positive CSCC patients compared with healthy females. Down-regulated SRA1 distinguished HPV-negative CSCC patients from HPV-positive CSCC patients and healthy females. In HPV-negative CSCC patients, miR-9 was up-regulated and inversely correlated with SRA1. In HPV-negative CSCC cells, SRA1 overexpression caused the down-regulated miR-9, while miR-9 overexpression failed to affect SRA1. Moreover, SRA1 overexpression caused decreased, while miR-9 overexpression caused increased proliferation, migration and invasion rates of cancer cells. In addition, miR-9 overexpression attenuated the effects of SRA1 overexpression. Therefore, SRA1 is down-regulated in HPV-negative CSCC and regulates cancer cell behaviors possibly by down-regulating miR-9.