Progression Of Colon Cancer Cells Research Articles

Prognostic value and chemotherapy response prediction of a proliferation essential gene signature in colon cancer.

Colon cancer is a common malignant tumor in the digestive tract. Exploring new treatment targets is of great significance for improving the survival rate of colon cancer patients. The present study mainly analyzes the impact of proliferation essential genes (PLEGs) on the prognosis and chemotherapy response of colon cancer patients, as well as identifying the expression and cellular functions of important PLEG. The DepMap database was utilized for identification of PLEG in colon cancer cells. Through DEGs screening, WGCNA, univariate cox regression survival analysis, and LASSO, a PLEG signature (PLEGs) model was constructed. The impact of PLEGs on the prognosis of colon cancer patients and their response to chemotherapy was further analyzed. Finally, we conducted a random forest analysis and implemented functional experiments to investigate the prominent PLEG that is linked to the development of colon cancer. Based on the expression and prognosis of PLEG, we constructed a PLEGs prognosis model which can effectively predict the prognosis of colon cancer patients and their response to chemotherapy treatment. Random forest analysis showed that UBA1 is a key PLEG in the progression of colon cancer. Immunohistochemistry results revealed that UBA1 protein is significantly upregulated in colon cancer tissues. Cell functional experiments demonstrated that knocking down UBA1 can inhibit the proliferation, invasion, and migration abilities of colon cancer cells. PLEGs have the potential to serve as predictive biomarkers for prognosis and chemotherapy response in colon cancer patients. Among the PLEG, UBA1 plays a prominent role in promoting the malignant progression of colon cancer cells.

Let-7b-5p inhibits colon cancer progression by prohibiting APC ubiquitination degradation and the Wnt pathway by targeting NKD1.

Naked cuticle homolog 1 (NKD1), which is expressed at low levels in many tumors, is considered an inhibitor of the Wnt/β-catenin pathway, but it is highly expressed in colon cancer and can promote colon cancer cell proliferation. miRNAs are involved in the occurrence and progression of many tumors. However, miRNAs that can regulate NKD1 and the mechanisms by which NKD1 regulates tumor progression remain ambiguous. This research aims to reveal the potential regulatory network of NKD1 in colon cancer. miRNA data downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed by bioinformatics to screen for potential miRNAs targeting NKD1. Let-7b-5p was found to inhibit proliferation, migration, and invasion of colon cancer cells targeting NKD1. Further studies suggested that let-7b-5p can modulate Wnt signaling activity, and the nuclear accumulation of β-catenin was significantly restrained by let-7b-5p through targeting NKD1. Moreover, NKD1 could prohibit the expression of the APC protein. Further studies manifested that NKD1 bound to APC and promoted the ubiquitination degradation of APC through restraining the expression of the deubiquitinating enzyme USP15 and blocking the combination between USP15 and APC. Functionally, NKD1 enhanced the proliferation and migration of colon cancer cells by inhibiting APC expression. This research revealed a novel mechanism by which the let-7b-5p-NKD1-APC-β-catenin signaling pathway inhibited colon cancer cell progression.

Regulation of Colon Cancer Cells Biology by Long Non-Coding RNA Metastasis Associated Lung Adenocarcinoma Transcript 1 (LncRNA MALAT1) via Targeting miR-184

Colon cancer remains a serious threat to human, as lncRNAs and miRNAs are found as crucial components for colon cancer progression and metastasis. But the role of lncRNA MALAT1 in colon cancer remains elusive. Herein, we aimed at investigating its function in the colon cancer and exploring the interaction between MALAT1 and miR-184. We collected tumor tissue specimens from patients with colon cancer and determined the expression of MALAT1 and miR-184 using RTqPCR. Functional experiment was established to detect the impact of MALAT1 siRNA or miR-184 inhibitor, followed by transwell assay and scratch experiment to assess colon cancer cell migration and invasion. Bioinformatics software and luciferase reporter system analyzed the targeting relationship between MALAT1 and miR-184. MALAT1 was up-regulated in colon cancer tissue, while miR-184 was poorly expressed and they were correlated with the clinicopathology of colon cancer ( P <0.05). miR-184 was indicated as the target miRNA of MALAT1. Moreover, silencing of MALAT1 up-regulatedthe expression of miR-184 when activating Caspase3 activity, inhibiting Bcl-2 expression, increasing Bax expression. And MALAT1 siRNA inhibited cancer cell migration and invasion ( P <0.05). However, transfection of miR-184 inhibitor abrogated these effectsinhibitor, when increasing MALAT1 expression. Collectively, we demonstrated that miR-184 is the target miRNA of Lnc-RNA MALAT1 and MALAT1 promotes colon cancer cell progression through inhibition of miR-184.

Transcription Factor FXR Activates DHRS9 to Inhibit the Cell Oxidative Phosphorylation and Suppress Colon Cancer Progression.

Colon cancer is a common gastrointestinal malignancy. It has been discovered that Farnesoid X receptor (FXR) plays an imperative regulatory role in multitype cancers in recent years. However, its regulatory mechanism in colon cancer has not been clearly explored. This study intended to explore the molecular regulatory mechanism of FXR and its downstream genes on the malignant progression of colon cancer. The mRNA and protein expression of FXR in colon cancer cells were measured by quantitative real-time polymerase chain reaction and Western blot. The effects of FXR on the biological function of colon cancer cells were measured by Cell Counting Kit-8, colony formation, and transwell assays. The downstream target gene of FXR was predicted by bioinformatics analysis and found to be associated with cellular oxidative phosphorylation. The binding relationship between FXR and its downstream gene dehydrogenase/reductase member 9 (DHRS9) was verified through luciferase reporter assay and chromatin immunoprecipitation assay. The changes of oxidative phosphorylation were detected by Western blot and oxygen consumption rate determination. The effect of FXR/DHRS9 axis on the malignant progression of colon cancer cells was further confirmed by rescue experiments. FXR was underexpressed in colon cancer tissues and cells, and overexpressing FXR could repress the malignant behaviors of colon cancer cells. Besides, DHRS9 was a downstream gene of FXR, and FXR/DHRS9 inhibited the deterioration of colon cancer through inhibiting oxidative phosphorylation. Moreover, promoting FXR expression in colon cancer cells could partially reverse the biological function changes caused by silencing DHRS9 expression. FXR inhibited the oxidative phosphorylation and inhibited the malignant progression of colon cancer cells via targeting DHRS9.

Hainanolide inhibits the progression of colon cancer via inducing the cell cycle arrest, cell apoptosis and activation of the MAPK signaling pathway

Hainanolide (HN) is a norditerpenoid metabolite extract from Cephalotaxus fortunei Hook. f. C. fortunei Hook. f. is renowned for the active alkaloids, such as harringtonine (HT) and homoharringtonin (HTT), which have been clinically used to treat chronic myeloid leukemia. Nowadays, diterpenoids, another important metabolite, attracted the attention of chemists. Among them, Hainanolide (HN), a cephalotane-type diterpenoid, has been proven to possess potent antitumor activities. However, the underlying therapeutic mechanisms of HN in anti-tumor have not been investigated yet. Our present study demonstrated that HN inhibited HCT-116 and HCT-15 cell proliferation in a dose- and time-dependent manner. Further studies demonstrated that HN can induce G2/M phase arrest and alter the Cdc25C/Cdc2/CyclinB1 proteins. Western blot indicated that HN promoted apoptosis by up-regulating Bax and down-regulated Bcl-2. And the caspase-3 and caspase-9 activities of HCT-116 and HCT-15 cells were increased. Transcriptome analysis is used to reveal the possible mechanism. Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested the genes were mainly enriched in the MAPK signaling pathway. Certainly, HN activates MAPK signaling pathway. In vivo, HN prevented the AOM/DSS-induced tumorigenesis of colon cancer in C57BL/6 mice. Our study indicated that HN inhibits the progression of colon cancer cells by blocking the cell cycle, inducing apoptosis, and activating the MAPK pathway. This study provides a theoretical and experimental scientific basis for future investigations of the antitumor effects of HN against colon cancer.

Identification and verification of the role of crucial genes through which methionine restriction inhibits the progression of colon cancer cells.

Studies have shown that methionine restriction (MR) can inhibit tumor progression, but its mechanism in colon cancer is unknown. Through DESeq2 and Edge analysis of the GSE72131 and GSE103602 datasets, 649 co-upregulated and 532 co-downregulated genes affected by MR were identified, respectively. Enrichment analysis showed that these genes were closely associated with tumor progression. Combined with the differentially expressed genes of colon cancer in The Cancer Genome Atlas database, MR affected 330 dysregulated genes in colon cancer. On this basis, a transcriptional regulatory and competing endogenous RNA network was established and F transcription factor 1 and microRNA 17-92a-1 Cluster Host Gene were identified as a key transcription factor and long non-coding RNA, respectively. In addition, four genes (FA Complementation Group I, Holliday Junction Recognition Protein, Karyopherin Subunit Alpha 2 and Kinesin Family Member 15) were identified by analyzing the relationship between dysregulated genes and overall survival. Finally, western blotting, reverse transcription-quantitative PCR, Transwell and other in vitro experiments verified that MR inhibits HCT116 colon cancer cell proliferation, metastasis and invasion, induces apoptosis and downregulates 6 hub genes. Collectively, the present study identified potential targets for MR to inhibit colon cancer progression and contributed to the clinical application of MR.

Long non-coding RNA LINC00511 facilitates colon cancer development through regulating microRNA-625-5p to target WEE1

The altered part of long non-coding RNA LINC00511 (LINC00511) is extensively discussed in malignancies. Finitely, the mechanism of LINC00511 in colon cancer (CC) development lacks thorough explorations. Hence, this work is started from the LINC00511-mediated microRNA (miR)-625-5p/WEE1 axis in the CC process. LINC00511, miR-625-5p, and WEE1 levels were tested in CC tissues and cells. Subcellular localization of LINC00511 was clarified. CC cells were transfected with oligonucleotides that altered LINC00511, and miR-625-5p expression to define their performance in CC cell progression. The tumorigenic ability of cells was verified in xenografted tumors. CC tissues and cells highly expressed LINC00511 and WEE1 and lowly expressed miR-625-5p. LINC00511 was mainly localized in the cytoplasm. Deleted LINC00511 or restored miR-625-5p delayed cellular growth in CC. LINC00511 sponged miR-625-5p to target WEE1. Silenced miR-625-5p mitigated the role of depleted LINC00511, while inhibited WEE1 rescued the effect of silenced miR-625-5p on the biological functions of CC cells. It is summarized that down-regulated LINC00511 obstructs tumorigenesis of CC through restoring miR-625-5p and silencing WEE1, consolidating a basal reference for CC-oriented therapy.

MiR-766-3p Suppresses Malignant Behaviors and Stimulates Apoptosis of Colon Cancer Cells via Targeting TGFBI.

Background MicroRNAs (miRNAs) can affect the progression of colon cancer cells. A variety of miRNAs, especially miR-766-3p, are proved to be abnormally expressed in colon cancer, but the molecular mechanism of miR-766-3p in this cancer has not yet been fully defined. Methods Differentially expressed genes in the TCGA-COAD dataset were searched through bioinformatics analysis. MiR-766-3p and TGFBI mRNA levels were measured by qRT-PCR. TGFBI protein expression was measured via Western blot. Targeting relation between miR-766-3p and TGFBI was investigated by dual-luciferase reporter gene assay. Cell proliferation, invasion migration, and apoptosis were detected by cell functional assays. Results MiR-766-3p was less expressed, while TGFBI was conspicuously highly expressed in colon cancer. MiR-766-3p high expression suppressed cell malignant behaviors and induced cell apoptosis in colon cancer. MiR-766-3p had a targeting relation with TGFBI verified by dual-luciferase assay. The cancer-suppressive impact of miR-766-3p overexpression was attenuated by overexpressing TGFBI. Conclusions MiR-766-3p/TGFBI axis suppressed malignant behaviors and facilitated apoptosis of colon cancer cells. MiR-766-3p may be an underlying target for colon cancer.

Ring finger 220 promotes the stemness and progression of colon cancer cells via Ubiquitin specific peptidase 22-BMI1 axis

ABSTRACT Colorectal cancer (CRC) is ranked as the third most common malignancy worldwide. Therefore, it is urgent to screen novel and effective molecular drug targets for colorectal cancer therapeutics. In this study, the specific role and related mechanism underlying Ring finger (RNF) 220 in colon cancer were investigated. Firstly, RT-PCR assay was used to compare differences between expression levels of RNF220 in colorectal tumor and normal tissues. Western blot and RT-PCR assays were applied to examine the protein levels of RNF220 in normal colonic mucosa and colorectal cancer cells. We found that RNF220 was upregulated in colorectal cancer in patients and cell models. RNF220 promoted the proliferation and migration, invasion of colorectal cancer cells through BrdU incorporation, clone formation, transwell and wound healing assays. Spheroid formation and western blot assays illustrated that RNF220 promoted the stemness of colorectal cancer cells. Moreover, we found that RNF220 regulated BMI1 expression through USP22 by western blot. Finally, we discovered that RNF220 facilitated tumor growth in vivo through establishment of subcutaneous xenograft tumor mice model. In conclusion, RNF220 promoted the stemness and progression of colon cancer cells via the USP22-BMI1 axis.

A short deletion in the DNA-binding domain of STAT3 suppresses growth and progression of colon cancer cells.

In this study, we investigated the effect of a short deletion in the DNA-binding domain of STAT3 (STAT3del) on the transcriptional activation of STAT3 target genes and its relationship with colon carcinogenesis. We used the CRISPR-CAS9 gene editing system to delete a short sequence encoding amino acids 400-411 in the DNA-binding domain (amino acid sequence: 317-567) from STAT3 gene in SW480, SW620 and HCT116 colon cancer cells. ChIP sequencing analysis showed that STAT3del occupancy was significantly reduced in 1029 genes and significantly increased in 475 genes compared to wild-type STAT3. The mutation altered the DNA motifs recognized by STAT3del as compared to the wild-type STAT3. We observed a strong correlation between expression of the STAT3 target genes and the loss or gain of STAT3del binding to their promoters. CCK-8, wound healing, and TUNEL assays showed reduced proliferation, migration, and survival of SW480, SW620 and HCT-116 cells expressing STAT3del as compared to the corresponding controls. These findings demonstrate that a short deletion in the DNA-binding domain of STAT3 alters its genome-wide DNA-binding and transcriptional profile of STAT3-target proteins, and suppresses the growth, progression and survival of colon cancer cells.

Targeting LncRNA EPIC1 to inhibit human colon cancer cell progression.

Long non-coding RNA EPIC1 (Lnc-EPIC1) binds MYC protein, which is essential for MYC function and expression of MYC target genes. The current study tested its expression and potential functions in human colon cancer cells. We show that Lnc-EPIC1 expression is elevated in human colon cancer tissues and primary human colon cancer cells. Whereas its expression is relatively low in normal colon tissues and colon epithelial cells. In the primary human colon cancer cells, Lnc-EPIC1 siRNA largely inhibited cancer cell growth, proliferation, migration and invasion. Further, Lnc-EPIC1 silencing induced significant apoptosis activation in colon cancer cells. Conversely, ectopic overexpression of Lnc-EPIC1 augmented colon cancer cell growth, proliferation, migration and invasion. RNA-immunoprecipitation and RNA pull-down results confirmed that Lnc-EPIC1 directly binds MYC protein in colon cancer cells. MYC target proteins, including cyclin A, cyclin D and CDK9, were downregulated with Lnc-EPIC1 silencing, but upregulated after Lnc-EPIC1 overexpression in colon cancer cells. Further Lnc-EPIC1 silencing or overexpression failed to alter functions of MYC-knockout colon cancer cells. Collectively, overexpressed Lnc-EPIC1 is important for the progression of human colon cancer cells.

CircTBL1XR1/miR-424 axis regulates Smad7 to promote the proliferation and metastasis of colorectal cancer.

This study analyzed the effect of circular RNA (circRNA), TBL1XR1, on the malignant progression of colon cancer cells and explored its possible molecular mechanism. The expression levels of circTBL1XR1 in colorectal cancer and paracancerous tissues were detected by quantitative real-time polymerase chain (qRT-PCR). Changes in circTBL1XR1 expression in normal intestinal epithelial cells and colon cancer cell lines were detected at the cellular level. LoVo and SW620 cells with the highest circTBL1XR1 expression were transfected with circTBL1XR1, and the transfection efficiency was verified by qRT-PCR. The effects of circTBL1XR1 on the proliferation, migration, and invasion of colon cancer cells were detected by MTT, Transwell migration, and invasion assay, and a subcutaneous tumor model. Target genes of circTBL1XR1 were verified by luciferase reporter assay. Expression levels of circTBL1XR1 target genes were detected by qRT-PCR and Western blotting. circTBL1XR1 was highly expressed in colon cancer patients. circTBL1XR1 expression in colon cancer cells was also higher than that in normal intestinal cells. In vivo and in vitro experimental results showed that overexpression of circTBL1XR1 enhanced the proliferation, migration, and invasion of colon cancer cells. After lowering circTBL1XR1, the ability of migration and invasion of colon cancer cells was significantly reduced. Bioinformatics retrieval and luciferase reporter gene assay confirmed that circTBL1XR1 can bind to microRNA-424 (miR-424) and that the Smad7 gene is the target gene of miR-424. circTBL1XR1 was highly expressed in colon cancer, and miR-424 was poorly expressed in colon cancer cells. circTBL1XR1 regulates the expression of Smad7 through miR-424, thereby affecting the malignant progression of colorectal cancer.

Sevoflurane suppresses cell viability and invasion and promotes cell apoptosis in colon cancer by modulating exosome‑mediated circ‑HMGCS1 via the miR‑34a‑5p/SGPP1 axis.

As a novel halogenated hydroxyl ether-inhaled general anesthetic, sevoflurane has been reported to affect the progression of diverse human cancers. In the present study, we aimed to explore the functions and underlying mechanisms of sevoflurane in colon cancer. MTT assay, flow cytometric analysis and Transwell assay were conducted to evaluate cell viability, apoptosis and invasion, respectively. Western blot analysis was performed to determine the protein level of sphingosine-1-phosphate phosphatase 1 (SGPP1). The morphology and size of exosomes were analyzed by TEM and NTA. The levels of circular RNA 3-hydroxy-3-methylglutaryl-CoA synthase 1 (circ-HMGCS1), microRNA (miR)-34a-5p and SGPP1 mRNA were examined by RT-qPCR. Dual-luciferase reporter and RNA RIP assays were utilized to explore the interaction between miR-34a-5p and circ-HMGCS1 or SGPP1. A murine xenograft model was established to investigate the effect of circ-HMGCS1 in vivo. As a result, it was determined that sevoflurane suppressed cell viability and invasion and induced apoptosis in colon cancer in a dose-dependent way. Exosomal circ-HMGCS1 was increased in the serums and cells of colon cancer patients. Circ-HMGCS1 was downregulated by sevoflurane treatment in colon cancer cells and circ-HMGCS1 overexpression could restore the effect of sevoflurane on colon cancer cell development. miR-34a-5p was a target of circ-HMGCS1 and miR-34a-5p inhibition reversed the effect of circ-HMGCS1 silencing on colon cancer cell progression. Moreover, circ-HMGCS1 knockdown suppressed SGPP1 expression via sponging miR-34a-5p. Knockdown of circ-HMGCS1 blocked tumor growth in vivo. In conclusion, sevoflurane inhibited colon cancer progression by modulating the exosome-transmitted circ-HMGCS1/miR-34a-5p/SGPP1 axis.

Garcinone C suppresses colon tumorigenesis through the Gli1-dependent hedgehog signaling pathway

BackgroundAlthough garcinone C, a natural xanthone derivative identified in the pericarp of Garcinia mangostana, has been demonstrated to exert different health beneficial activities in oxidative stress and β-amyloid aggregation, the role of garcinone C in colon tumorigenesis has not been investigated. In addition, aberrant Hedgehog (Hh) signaling activation is associated with tumorigenesis including colon cancer. Here, we hypothesized that garcinone C can prevent colon tumorigenesis through regulating the Hh signaling pathway. MethodColony formation assay and flow cytometry were used to evaluate the effect of garcinone C on the proliferation and cell cycle progression of colon cancer cells. Protein expression of cell cycle related markers and Hh/Gli1 signaling mediators were determined. The regulatory effect of orally administered garcinone C on the Hh/Gli1 signaling pathway and colon tumorigenesis was evaluated in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colon cancer animal model. ResultsGarcinone C suppressed the proliferation of colon cancer cells, induced G0/G1 cell cycle arrest, as well as regulated the expression of cell cycle-related markers such as cyclin D1, cyclin E, CDK6, and p21. Garcinone C inhibited the expression of Gli1, a key mediator of Hedgehog signaling, and protein kinase B (AKT) phosphorylation in Smo-independent colon cancer cells. In the AOM/DSS-induced colon tumorigenesis model, garcinone C significantly inhibited tumor development, regulated the expression of cell cycle markers and Gli1, and reduced AKT phosphorylation in colon tumor tissues, which is consistent with our in vitro results. ConclusionGarcinone C can suppress colon tumorigenesis in vitro and in vivo through Gli1-dependent non-canonical Hedgehog signaling, suggesting that it may serve as a potent chemopreventive agent against colon tumorigenesis.

The FBW7-MCL-1 axis is key in M1 and M2 macrophage-related colon cancer cell progression: validating the immunotherapeutic value of targeting PI3K\u03b3

Colorectal cancer is a devastating disease with a low 5-year survival rate. Recently, many researchers have studied the mechanisms of tumor progression related to the tumor microenvironment. Here, we addressed the prognostic value of tumor-associated macrophages (TAMs) using a total of 232 CRC patient tissue samples and investigated the mechanisms underlying TAM-related colon cancer progression with respect to PI3Kγ regulation using in vitro, in vivo, and ex vivo approaches. Patients with M2/M1 < 3 had significantly improved progression-free survival and overall survival compared with patients with M2/M1 > 3. M1 and M2 macrophages elicited opposite effects on colon cancer progression via the FBW7-MCL-1 axis. Blocking macrophage PI3Kγ had cytotoxic effects on colon cancer cells and inhibited epithelial–mesenchymal transition features by regulating the FBW7-MCL-1 axis. The results of this study suggest that macrophage PI3Kγ may be a promising target for immunotherapy in colon cancer.

NEAT1 promotes colon cancer progression through sponging miR-495-3p and activating CDK6 in vitro and in vivo.

Recently, increasing evidence has indicated lncRNAs are powerful regulators in the progression of multiple tumors. Dysregulation of lncRNA NEAT1 has been recognized in many cancer types. Meanwhile, the studies on NEAT1 function have suggested that NEAT1 can serve as a crucial oncogene. Nevertheless, the investigation of NEAT1 in colon cancer is still few. In our study, the function of NEAT1 was studied in colon cancer. As we observed, NEAT1 level was obviously elevated in colon cancer cells. Then, HCT-116 and SW620 cells were stably infected with shRNA-NEAT1 for 48 hr. As exhibited, silence of NEAT1 could greatly repress colon cancer cell progression. Apoptosis of colon cancer cells was triggered and the cell cycle progression was remarkably inhibited by downregulation of NEAT1. Interestingly, as exhibited, miR-495-3p was obviously decreased in colon cancer cells and it significantly suppressed colon cancer progression. Subsequently, miR-495-3p was predicted as a target of NEAT1. CDK6 was speculated as the target of miR-495-3p and miR-495-3p modulated its expression negatively. Finally, it was indicated that NEAT1 promoted colon cancer development through modulating miR-495-3p and CDK6 in vivo. Taken these together, we reported that NEAT1 could sponge miR-495-3p to contribute to colon cancer progression through activating CDK6.

Abstract 2061: Genipin inhibits invasion and migration of colon cancer cells by suppression of HIF1α accumulation and VEGF expression

Abstract Expression of hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) is known to play an important role in cancer progression in various cancer cell lines. Although genipin, a constituent of Gardenia fruit, has shown to have anti-tumor activity, its role in suppression of HIF-1 protein and downstream genes has yet to be clarified. We examined the effect of genipin on intracellular level of HIF-1α and extracellular level of VEGF proteins using colon cancer cell line HCT116. We observed genipin suppressed accumulation of HIF-1α under hypoxia in various cancer cell lines including HCT116. We found out suppressed accumulation of HIF-1α occurred through modulation of protein degradation. Genipin was also observed to suppress expression of VEGF and invasion of colon cancer cells through blocking of the ERK signaling pathway. Taken together, our results provide a new insight into the potential role of genipin in suppressing cancer progression of colon cancer cells. Citation Format: Dae-Hee Lee, Sang-Choul Oh, Suk-young Lee, Hong Jun Kim. Genipin inhibits invasion and migration of colon cancer cells by suppression of HIF1α accumulation and VEGF expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2061.

LncRNA MALAT1 induces colon cancer development by regulating miR-129-5p/HMGB1 axis.

Recent studies have exhibited significant roles of lncRNAs in various tumors' development, including colon cancer. Our study focused on the biological roles of lncRNA MALAT1 in colon cancer. In our study, it was demonstrated that MALAT1 was upregulated in human colon cancer cell lines including Lovo, HCT116, SW480, and HT29 cells compared to the normal human intestinal epithelial HIEC cells. Moreover, we observed that miR-129-5p was downregulated in colon cancer cells with a significant increase of HMGB1 expression. Inhibition of MALAT1 can inhibit the proliferation of colon cancer SW480 and HCT116 cells and next, bioinformatics analysis was used to predict the target microRNA of MALAT1. miR-129-5p was identified and confirmed as a direct regulator of MALAT1 and it was shown that miR-129-5p mimics were able to restrain the progression of colon cancer cells. In addition, high motility group box protein 1 (HMGB1), was predicted as a mRNA target of miR-129-5p. Furthermore, we found that MALAT1 exerted its biological functions through regulating HMGB1 by sponging miR-129-5p in vitro. Silencing MALAT1 greatly inhibited HMGB1 expression which can be reversed by miR-129-5p inhibitors. It was indicated in our investigation that MALAT1 may serve as a competing endogenous lncRNA (ceRNA) to mediate HMGB1 by sponging miR-129-5p in colon cancer. Taken together, our results indicated that MALAT1/miR-129-5p/HMGB1 axis could be provided as an important prognostic biomarker in colon cancer development.

Influence of ALA-mediated photodynamic therapy on secretion of interleukins 6, 8 and 10 by colon cancer cells in vitro.

Photodynamic therapy has apart from a direct cytotoxic effect also immunomodulatory properties. The aim of our study was to investigate how photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) in sublethal doses influences the secretion of interleukins 6, 8 and 10 from colon cancer cells in vitro. We used two human colon cancer cell lines SW480 and SW620 of different malignancies which were treated with a sublethal PDT protocol. Determination of interleukins was carried out using the Bio- Plex Assay Pro™ kit on the Bio- Plex Suspension Array System. Sublethal ALA-PDT did not affect IL-6 secretion by SW480 cells, but caused a 40% decrease of IL-6 release by the SW620 cell line. It increased IL-8 secretion in both, the SW480 and SW620 cell lines, by 23% and 46%, respectively, and decreased the production of IL-10 (25% in SW480 and 32% in SW620 cells). ALA-PDT in sublethal doses might influence colon cancer cell's progression and invasion by reducing the secretion of IL-6, IL-10 and increasing the IL-8 concentration with higher values in the more malignant cell line.

Abstract 312: Anti-proliferative effects of cinnamon extract in colon cancer

Abstract Colon cancer is the third most lethal cancer worldwide, and is estimated to cause 49,190 cancer-related deaths in the U.S. in 2016 alone. Current treatments for colon cancer are limited in their capacity to target tumor cells employing adaptive mechanisms necessary for survival and proliferation, often resulting in poor prognosis. Therefore, it is critical to develop novel target-specific therapeutic approaches with minimal cytotoxicity to normal cells, in order to mitigate potential side effects. Proanthocyanidins represent a subclass of flavonoids, which have been widely investigated for their chemopreventive and therapeutic potential. Cinnamtannin B-1 (CTB-1) is a proanthocyanidin shown to have anti-cancer effects in several cancers, but its anti-cancer potential in colon cancer has not been tested. Hence, the focus of this study was to determine the anticancer effects of CTB-1 in colon cancer. Our results show that CTB-1 treatment significantly decreases the cell viability and proliferation of DLD-1 and COLO 201 human colon cancer cells in a time and dose-dependent manner. In addition, CTB-1 treatment modulated the cell cycle progression of colon cancer cells via G2/M arrest, coupled with a reduction of cells in the S phase. The expression and/or phosphorylation of key molecules involved in apoptosis and cell cycle progression were also modulated in response to CTB-1 treatment. Collectively, these findings, for the first time, shed light on the anti-proliferative effects of CTB-1 in colon cancer, and further demonstrate its potential as a novel therapeutic/preventive agent. Citation Format: Patrick P. Carriere, Hina Mir, Neeraj Kapur, Clarence E. Clark, Shailesh Singh. Anti-proliferative effects of cinnamon extract in colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 312. doi:10.1158/1538-7445.AM2017-312