Invasion Of Colon Cancer Cells Research Articles

MiR-509-3-5p inhibits colon cancer malignancy by suppressing GTSE1

BackgroundThe overarching goal of this research was to identify the effect of miR-509-3-5p on colon cancer (CC) and its interaction with potential target gene GTSE1 in CC. MethodsThe miR-509-3-5p expression was ascertained after performing qRT-PCR analyses, and the ability of GTSE1 to influence this microRNA was detected after carrying out RNA pull-down assay. CCK-8 assay kit was first employed to determine the proliferation of the cells. To examine the migration and invasion level of HCT116 and SW480 cells, cell wound healing and transwell assay were later performed. After constructing luciferase reporter plasmids, luciferase reporter assay was used to confirm the impacts of miR-509-3-5p on GTSE1 in HCT116 and SW480 cells. ResultsWe found that miR-509-3-5p expression reduced in CC, and its overexpression inhibited the proliferation, migration and invasion of CC cells. We later discovered that miR-509-3-5p could target GTSE1 that was then proved to be an oncogene in CC. ConclusionOur study uncovered that miR-509-3-5p regulated CC malignancy by suppressing target gene GTSE1.

LINC01287 facilitates proliferation, migration, invasion and EMT of colon cancer cells via miR-4500/MAP3K13 pathway

BackgroundAccumulated studies indicate that aberrant expression of long noncoding RNAs (lncRNAs) is associated with tumorigenesis and progression of colon cancer. In the present study, long intergenic non-protein coding RNA 1287 (LINC01287) was identified to up-regulate in colon cancer by transcriptome RNA-sequencing, but the exact function remained unclear.MethodsTranscriptome RNA-sequencing was conducted to identify dysregulated lncRNAs. Expression of LINC01287 was evaluated by real-time quantitative PCR. The downstream targets of LINC01287 and miR-4500 were verified by luciferase reporter assay, pull down assay and western blot. The potential functions of LINC01287 were evaluated by cell viability assay, colony formation assay, soft agar assay, flow cytometry, transwell migration and invasion assay, and tumor xenograft growth in colon cancer cells.ResultsOur results indicated that LINC01287 was up-regulated in colon cancer patients. High LINC01287 expression was associated with advanced TNM stage, lymph node metastasis, distant metastasis and shorter overall survival. Knockdown of LINC01287 inhibited cell growth, colony formation in plates and soft agar, transwell cell migration and invasion, and epithelial-mesenchymal transition (EMT) of colon cancer cells, while LINC01287 overexpression had contrary effects. In addition, LINC01287 mediated MAP3K13 expression by sponging miR-4500, thus promoted NF-κB p65 phosphorylation. Restored MAP3K13 expression or miR-4500 knockdown partially abrogated the effects of silencing LINC01287 in colon cancer cells.ConclusionOur findings demonstrated that the LINC01287/miR-4500/MAP3K13 axis promoted progression of colon cancer. Therefore, LINC01287 might be a potential therapeutic target and prognostic marker for colon cancer patients.

Targeting FHL2-E-cadherin axis by miR-340-5p attenuates colon cancer cell migration and invasion.

Convincing data has suggested that four and a half LIM domain 2 protein (FHL2) serves a key function in cancer cell metastasis and that microRNA (miR)-340-5p can regulate cancer cell migration. The current study hypothesized that targeting FHL2 expression by miR-340-5p in colon cancer may attenuate colon cancer cell migration and invasion. FHL2 expression was therefore assessed in colon cancer microarray datasets using Qlucore omics explorer as well as in HT-29 and AZ-97 colon cancer cell lines via reverse transcription-quantitative PCR (RT-qPCR). Colon cancer cell migration and invasion were evaluated in the presence of miR-340-5p mimic, mimic control or mimic with a target site blocker. Confocal microscopy and RT-qPCR were subsequently performed to assess FHL2, E-cadherin (E-cad) protein and mRNA expression in colon cancer cells. Microarray dataset analysis revealed that FHL2 expression was lower in primary colon cancer cells compared with normal colonic mucosa. It was revealed that the expression of miR-340-5p and FHL2 were inversely related in serum-grown and low-serum conditions in HT-29 and AZ-97 cells. Short-time serum exposure to low-serum grown cells induced FHL2 expression. Transfection of HT-29 cells with miR-340-5p mimic not only decreased serum-induced expression of FHL2 but also decreased cancer cell migration and invasion. Bioinformatics analysis revealed that FHL2 mRNA had one putative binding site for miR-340-5p at the 3-untranslated region. Blocking of the target site using a specific blocker reverted miR-340-5p mimic-induced inhibition of FHL2 expression and cancer cell migration and invasion. Confocal microscopy confirmed that the reduction of FHL2 expression by miR-340-5p mimic also reversed serum-induced E-cad disruption and that the target site blocker abrogated the effect of miR-340-5p. The current results suggested that miR-340-5p could be used to antagonize colon cancer cell metastasis by targeting the FHL2-E-cad axis.

C-C motif chemokine ligand 14 inhibited colon cancer cell proliferation and invasion through suppressing M2 polarization of tumor-associated macrophages.

Colon cancer is one of the most common cancers with a high incidence and high mortality. Chemokines play a crucial role in the development of cancer. Here, qRT-PCR was performed to detect gene expression. Western blot and immunohistochemistry were implemented to examine the expression of C-C motif chemokine ligand 14 (CCL14) in colon tumors. Besides, the expression of CD68 and CD206 in tumors was measured by immunohistochemistry. The percentages of M1- and M2-polarized macrophages were detected by flow cytometry. Furthermore, CCK-8 assay was performed to detect cell proliferation, and Transwell assay for cell invasion. CCL14 was decreased in both colon tumors and colon cancer cells, and many tumor-associated macrophages (TAMs) infiltrated into the tumor. An increase CCL14 inhibited colon cancer cell proliferation. Importantly, CCL14 promoted THP-1 to M1 polarization induced by LPS and IFN-γ, and inhibited THP-1 to M2 polarization induced by IL-4 and IL-13. Besides, CCL14 enhanced the inhibition of M1-polarized macrophages to colon cancer cell proliferation and invasion, and reversed the promotion of M2-polarized macrophages to cell proliferation and invasion. Our data demonstrated that CCL14 inhibited the proliferation and invasion of colon cancer cells through suppressing the formation of M2-like TAMs.

Xanthatin inhibits human colon cancer cells progression via mTOR signaling mediated energy metabolism alteration.

Tumor cells exhibit higher glycolysis and rely on abnormal energy metabolism to produce ATP, which is essential for cell proliferation and migration. Abnormal energy metabolism inhibition is considered a promising tumor treatment strategy. Xanthatin is an active sesquiterpene lactone isolated from Xanthium strumarium L. This study evaluated the effect of xanthatin on the energy metabolism of human colon cancer cells. The results showed that xanthatin significantly inhibited the migration and invasion of human HT-29 and HCT-116 colon cancer cells. We found that xanthatin effectively reduced the production of ATP and promoted the accumulation of lactate. Xanthatin inhibited glycolysis which may be related to the reduction of glucose transporter 1 (Glut1) and monocarboxylate transporter 4 (MCT4) mRNA and protein levels. Concomitantly, xanthatin promoted complex II activity and oxidative phosphorylation (OXPHOS), resulting in mitochondrial damage and cell death in HT-29 cells. Furthermore, xanthatin inhibited the phosphorylation of mTOR, the phosphorylation of 4E-binding protein 1 (4E-BP1) and c-myc in HT-29 cells. Moreover, rapamycin, a mTOR inhibitor, could enhance the cytotoxicity effect in xanthatin treated HT-29 cells. Additionally, HT-29 cells transfected with si-mTOR aggravated xanthatin induced cell viability inhibition. Based on these results, we observed that the effect of xanthatin on energy metabolism may be related to its inhibition of the mTOR signaling pathway. Collectively, this study provides important insights into xanthatin's anticancer effect, which occurs by regulation of the energy metabolism of human colon cancer cells, and suggest that xanthatin has potential as a botanical drug against abnormal tumor energy metabolism.

Egr‑1 inhibits colon cancer cell proliferation, migration and invasion via regulating CDKL1 at the transcriptional level.

Colon cancer is one of the most common malignant tumors worldwide, and the molecular mechanisms involved in the oncogenesis and progression of colon cancer remain unclear. Early growth response 1 (Egr‑1) is a transcription factor that is closely associated with several tumor processes; however, its role in colon cancer is unknown. The present study aimed to explore the function and mechanism of transcription factor Egr‑1 in colon cancer progression. The association between Egr‑1 expression and the survival of patients with colon cancer was analyzed. Transwell assay was used to measure the migration and invasion of colon cancer cells. Cell Counting Kit‑8 assay was used to evaluate the cell proliferative ability. Reverse transcription‑quantitative PCR and western blot assays were used to identify whether Egr‑1 could regulate cyclin‑dependent kinase‑like 1 (CDKL1). Luciferase and chromatin immunoprecipitation assays were used to detect the mechanism by which Egr‑1 regulated CDKL1. Based on The Cancer Genome Atlas database, it was found that low Egr‑1 expression was associated with a poor prognosis in patients with colon cancer. Furthermore, overexpression of Egr‑1 inhibited colon cancer cell proliferation, migration, and invasion, whereas knockdown of Egr‑1 increased colon cancer cell proliferation, migration and invasion. Additionally, overexpression of Egr‑1‑induced cell proliferation, migration and invasion were reversed by overexpression of CDKL1. Furthermore, it was demonstrated that Egr‑1 regulated CDKL1 expression at the transcriptional level. The present study illustrated the mechanism of Egr‑1 regulating CDKL1, by which Egr‑1 affected colon cancer cell proliferation, migration and invasion. The current findings suggested that Egr‑1/CDKL1 may be a new promising target for the treatment of colon cancer.

Folic Acid-Targeted Paclitaxel-Polymer Conjugates Exert Selective Cytotoxicity and Modulate Invasiveness of Colon Cancer Cells.

Although selective tumor delivery of anticancer drugs has been sought by exploiting either passive targeting or by ligand-mediated targeting, a selective anticancer therapy remains an unmet medical need. Despite the advances which have been achieved by nanomedicines, nanosystems such as polymer-drug conjugates still miss the goal of clinical efficacy. In this study, we demonstrated that polymer-drug conjugates require a thoroughly chemical design and the right targeting agent/polymer ratio to be selective and effective towards cancer cells. In particular, two PEG conjugates carrying paclitaxel and targeted with different folic acid (FA)/PEG ratios (one or three) were investigated. The cytotoxicity study in positive (HT-29) and negative (HCT-15) FA receptor (FR)-cell lines demonstrated that the conjugates with one or three FAs were 4- or 28-fold more active in HT-29 cells, respectively. The higher activity of the 3-FA conjugate was confirmed by its strong impact on cell cycle arrest. Furthermore, FA targeting had a clear effect on migration and invasiveness of HT-29 cells, which were significantly reduced by both conjugates. Interestingly, the 3-FA conjugate showed also an improved pharmacokinetic profile in mice. The results of this study indicate that thorough investigations are needed to optimize and tune drug delivery and achieve the desired selectivity and activity towards cancer cells.

Eupatilin Impacts on the Progression of Colon Cancer by Mitochondria Dysfunction and Oxidative Stress

Colon cancer is one of the most frequently diagnosed cancer types. Some colon cancer cases resist standard anticancer drugs. Therefore, many studies have focused on developing therapeutic supplements using natural products with low side effects and broad physiological activity. Eupatilin is a flavonoid that is mainly extracted from artemisia and promotes apoptosis in numerous cancer types. However, since the current understanding of its physiological mechanisms on colon cancer cells is insufficient, we investigated how eupatilin affects the growth of two colon cancer cell lines, namely HCT116 and HT29. Our results showed that eupatilin inhibits cell viability and induces apoptosis accompanied by mitochondrial depolarization. It also induces oxidative stress in colon cancer cells and regulates the expression of proteins involved in the endoplasmic reticulum stress and autophagic process. Moreover, eupatilin may target the PI3K/AKT and mitogen-activated protein kinase (MAPK) signaling pathways in colon cancer cells. It also prevents colon cancer cell invasion. Furthermore, eupatilin has a synergistic effect with 5-fluorouracil (5-FU; a standard anticancer drug) on 5-FU-resistant HCT116 cells. These results suggest that eupatilin can be developed as an adjuvant to enhance traditional anticancer drugs in colon cancer.

Study on effects of miR-141-3p in proliferation, migration, invasion and apoptosis of colon cancer cells by inhibiting Bcl2.

This study aimed to investigate the relationship between miR-141-3p and B lymphocyte-2 gene (Bcl2) gene and its biological behavior on colon cancer cell line SW480. qRT-PCR was used to detect the expression level of miR-141-3p in colon cancer tissues and adjacent tissues, as well as in colon cancer cell line and normal human colonic epithelial cell line FHC. MTT assay, wound assay, and Transwell demonstrated the effects of miR-141-3p on colon cancer proliferation, migration and invasion. Targetscan7.1 predictive software and dual luciferase reporter assays were used to detect the targeted regulation of miR-141-3p on the apoptosis-related gene Bcl2. MTT assay, wound assay, Transwell and flow cytometry were used to detect the effect of Bcl2 on miR-141-3p on colon cancer proliferation, migration, invasion and apoptosis. Compared with adjacent tissues, the expression of miR-141-3p in colon cancer tissues was significantly down-regulated. Colon cancer patients with low expression of miR-141-3p had poorer prognosis. Compared with normal colonic epithelial cells, miR-141-3p expression was significantly down-regulated in colon cancer cell lines, and overexpression of miR-141-3p significantly attenuated the proliferation, migration and invasion of colon cancer cells. Knockdown of miR-141-3p significantly promoted the proliferation, migration and invasion of colon cancer cells. miR-141-3p targets the negative regulation of Bcl2. Knockdown of Bcl2 significantly attenuated the promotion of miR-141-3p inhibitor on proliferation, migration and invasion of colon cancer cells and inhibition of apoptosis. Knockdown of Bcl2 significantly enhanced the inhibition effect of miR-141-3p inhibitor on proliferation, migration and invasion of colon cancer cells. In conclusion, miR-141-3p can inhibit the cancer by regulating Bcl2, and miR-141-3p has the potential to become a potential therapeutic target for colon cancer.

Retraction.

Retraction: "MicroRNA-204-3p represses colon cancer cells proliferation, migration, and invasion by targeting HMGA2," by Xiangpeng Xi, Mujian Teng, Liang Zhang, Lijian Xia, Jingbo Chen, Zhonghui Cui, J Cell Physiol. 2020; 1330-1338: The above article, published online on 08 July 2019 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/full/10.1002/jcp.29050), has been retracted by agreement between the journal's Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. Several flaws and inconsistencies between results presented and experimental methods described were found, the editors consider the conclusions of this article to be invalid. The authors collaborated in the investigation initially, but were not available for a final confirmation of the retraction.

INHBA promotes the proliferation, migration and invasion of colon cancer cells through the upregulation of VCAN.

ObjectiveColon cancer has high morbidity and mortality rates, and proliferation, invasion and migration play an important role in colon cancer progression. Here, the effects of inhibin subunit beta A (INHBA) on cell proliferation, invasion and migration were investigated.MethodsThe UALCAN database was used to assess INHBA expression in colon cancer tissues and predict the survival of patients with high and low INHBA expression. The relevant proteins were detected by RT-qPCR and western blot. Cell transfection was performed to overexpress or inhibit INHBA and versican (VCAN). The high correlation between INHBA and VCAN found through LinkedOmics and StarBase databases was verified by immunoprecipitation assays. Cell proliferation was detected by cell counting kit-8 and colony formation assays. Wound healing and Transwell assays were used to assess migration and invasion.ResultsINHBA expression was upregulated in colon cancer tissues and cells. INHBA inhibition impaired the proliferation, migration and invasion of these cells. In addition, we confirmed the correlation between INHBA and VCAN in colon cancer cells. Finally, we found that INHBA interference inhibited the aggressive behavior of colon cancer cells by downregulating VCAN.ConclusionINHBA promotes the proliferation, migration and invasion of colon cancer cells through the upregulation of VCAN.

Molecular mechanism of miR-34b-5p and RNA binding protein HuR binding to lncRNA OIP5-AS1 in colon cancer cells.

Colon cancer (CC) is a leading cause of cancer-related death. Long non-coding RNA OIP5-AS1 (lncRNA OIP5-AS1) expression pattern has been studied in many cancers. We aimed to identify the mechanism of lncRNA OIP5-AS1 in CC development. OIP5-AS1 expression pattern in CC tissues and cells was detected and the relation between OIP5-AS1 level and CC prognosis was analyzed. The proliferation, migration and invasion of CC cells were detected after silencing or overexpression of OIP5-AS1. Tumor xenograft in nude mice was established to verify the effect of OIP5-AS1 in vivo. The interaction between HuR protein and OIP5-AS1 and the interaction of miR-34b-5p with HuR and OIP5-AS1 were measured. OIP5-AS1 was highly expressed in CC and associated with poor prognosis. Silencing OIP5-AS1 inhibited CC cell malignant behaviors and inhibited the growth rate and tumor weight. In the mechanism, HuR bound to OIP5-AS1 and stabilized OIP5-AS1 expression. Both miR-34-5p and HuR bind to OIP5 and oppositely affect its expression. miR-34b-5p inhibited the proliferation and invasion of CC cells by inhibiting OIP5-AS1 and PI3K/Akt pathway. miR-34b-5p inhibited CC growth by inhibiting OIP5-AS1. Collectively, miR-34b-5p targets HuR and miR-34b-5p binds to OIP5-AS1 with HuR, thus inhibiting OIP5-AS1 and PI3K/Akt pathway and CC progression.

MTBP promoted the proliferation, migration and invasion of colon cancer cells by activating the expression of ZEB2

ABSTRACT Colon cancer is a malignant tumor that seriously affects human health. Recently, studies revealed that the expression of MTBP enhanced the proliferation and metastasis of many types of cancer cells. And the data also showed that MTBP has the potential to regulate the expression of ZEB2. However, it is unclear whether MTBP can affect the proliferation, migration and invasion of colon cancer cells by modulating the expression of ZEB2. In this study, we established the MTBP overexpression and knockdown colon cancer cells with the transfection. Next, CCK-8 and transwell assays were carried out to determine the changes of the proliferation and invasion of colon cancer cells, respectively. After that, we overexpressed the ZEB2 in these MTBP knockdown colon cancer cells. Finally, the invasion and migration of these cells were detected with the same methods. We revealed that overexpression of MTBP enhanced the proliferation and invasion of colon cancer cells. Moreover, suppression of MTBP repressed the proliferation, migration and invasion of colon cancer cells. Furthermore, MTBP promoted the expression of ZEB2. The overexpression of ZEB2 abolished the MTBP knockdown induced inhibition of the migration and invasion of colon cancer cells. These results implied that MTBP enhanced the proliferation, migration and invasion of colon cancer cells by activating the expression of ZEB2.

XIAP-AS1 is a New Long Non Coding RNA

Dysregulation of long non-coding RNAs (lncRNAs) is reported to be associated with the development and progression of various cancers. XIAP-AS1 is a novel lncRNA. It has been shown that XIAP-AS1 is transcribed from the first intron of the complementary strand of the XIAP gene. XIAP-AS1 is located primarily in the nucleus. LncRNA XIAP-AS1 can regulate apoptosis in gastric cancer and might serve as a potential oncogene for colon cancer. Sp1 is a responsible transcription factor for transcription of the XIAP gene. XIAP-AS1 RNA interacts with Sp1 and thereby participates in XIAP transcription. XIAP-AS1 knockingdown decreases the binding of Sp1 to the promoter region of XIAP. In gastric tumor cells, XIAP-AS1 knockdown promotes tumor necrosis factor (TNF)- related apoptosis-inducing ligand (TRAIL)-induced apoptosis. XIAP-AS1 knockdown blockes cell invasion of colon cancer cells by regulating the expression of EMT markers, such as E-cadherin, ZO-1, vimentin, and N-cadherin. Moreover, XIAP-AS1 knockdown significantly reduces STAT3 phosphorylation. XIAP-AS1 interacts with Sp1 and is involved in XIAP transcription. In gastric cancer cells, XIAP-AS1 is a potential target for TRAIL-induced apoptosis. XIAP-AS1 is significantly increased in CRC tissues and moreover its expression showes a positive correlation with TNM stage and cumulative survival rate of CRC. In this review, we focus on the importance of new lncRNA XIAP-AS1 in tumorigenesis, as it functions in apoptosis.

Hyperglycemia Promotes Liver Metastasis of Colorectal Cancer via Upregulation of Integrin αvβ6.

BackgroundDiabetes is related to higher risk of multiple cancers. This study aimed to explore the effect and mechanism of diabetes on liver metastasis of CRC.Material/MethodsOverall and liver metastasis-free survival in diabetic and non-diabetic CRC patients were compared by Kaplan-Meier analysis. Expression of αvβ6 was detected by immunohistochemistry in clinical specimens. Effects of hyperglycemia on αvβ6 expression in colon cancer cells were assessed by western blot, real-time PCR, and flowcytometry. Effects of hyperglycemia on migration and invasion were demonstrated by Transwell assay. Expression and activity of MMP-9 and MMP-2 were determined by real-time PCR and gelatin zymography. Liver metastatic nodules were counted and β6 expression was detected by western blot in a liver metastasis mouse model.ResultsCRC patients with diabetes had poorer overall and liver metastasis-free survival, and diabetes was associated with higher αvβ6 expression in CRC specimens. Hyperglycemia promoted the invasion and migration of colon cancer cells, and upregulated the expression and activity of MMP-9, which were attenuated by inhibition of αvβ6. Hyperglycemia upregulated the expression of β6 and cell surface expression of αvβ6, which was reduced by ERK inhibitor. The in vitro results were confirmed in vivo in the mouse model.ConclusionsOur study demonstrated the enhancing effect of hyperglycemia on liver metastasis of CRC, and showed that αvβ6 was involved in this process, suggesting that control of glucose levels and inhibition of αvβ6 can reduce the risk of liver metastasis in diabetic CRC patients.

TrkB/C-induced HOXC6 activation enhances the ADAM8-mediated metastasis of chemoresistant colon cancer cells.

The abnormal expression of tropomyosin receptor kinase(Trk) serves an important role in the promotion of cancer progression. HomeoboxC6(HOXC6) and Adisintegrin and metalloproteinase domain‑containing8(ADAM8) are associated with the invasiveness of cancer cells. However, the exact relationship between these molecules and their downstream signaling pathways in chemoresistant colon cancer cells are largely unknown. Therefore, the current study investigated the association between TrkB/C with HOXC6 and ADAM8 in the induction of drug‑resistant colon cancer cell metastasis. The results demonstrated that chemoresistant colon cancer cells exhibited upregulated TrkB/C, HOXC6 and ADAM8 expression. Additionally, but also chemoresistant colon cancer cells demonstrated higher migratory activities compared with parent colon cancer cells. The pharmacological inhibition of TrkB/C activity reduced the phosphorylation of mitogen‑activated protein kinase kinase/ERK and subsequently suppressed HOXC6 and ADAM8 expression. In addition, gene silencing of HOXC6 inhibited ADAM8 and MMP activity, and inhibited the migration and invasion of drug‑resistant cancer cells. However, the targeted downregulation of ADAM8 using small interfering RNA failed to suppress TrkB/C‑associated ERK‑mediated HOXC6 signaling activity. Furthermore, pre‑treatment with ADAM10‑ and ADAM17‑specific inhibitors had no effect on attenuating the invasiveness of chemoresistant colon cancer cells. The results indicated that TrkB/C‑mediated ERK activation serves an important role in the metastasis of drug‑resistant colon cancer cells through the regulation of HOXC6/ADAM8 activity.

Retracted] H19 promotes the migration and invasion of colon cancer by sponging miR‑138 to upregulate the expression of HMGA1.

Following the publication of this paper, it was drawn to our attention by an interested reader that a row of tumour images featured in Fig.5A of the above paper were strikingly similar to those featured in Fig.7A of an article appearing in Oncology Research [Zhang X, Gao F, Zhou L, Wang H, ShiG and TanX: UCA1 regulates the growth and metastasis of pancreatic cancer by sponging miR‑135a. Oncol Res 25:1529‑1541, 2017]. Furthermore, similarities in the data were also identified comparing Fig.4A in the above paper with Fig.6A in the same paper published in Oncology Research by Zhang etal. Finally, immunohistochemistry data featured in Fig.5G were strikingly similar to data featured in Fig.7G in the following article [Li Y, Luo H, Xiao N, Duan J WangZ and WangS:Long noncoding RNA SChLAP1 accelerates the proliferation and metastasis of prostate cancer via targeting miR‑198 and promoting the MAPK1 pathway. Oncol Res 26:131‑143, 2018]. The Editor asked the authors for an explanation to account for the appearance of strikingly similar data in their paper independently, although the authors never responded within a reasonable time to confirm that the paper should be retracted. The Editor has therefore made the executive decision to retract this paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in International Journal of Oncology 50: 1801‑1809, 2017; DOI: 10.3892/ijo.2017.3941].

Downregulation of OIP5-AS1 affects proNGF-induced pancreatic cancer metastasis by inhibiting p75NTR levels.

We aimed to explore the mechanism by which long non-coding RNA (lncRNA) OIP5-AS1 affects proNGF (precursor nerve growth factor)-induced pancreatic cancer metastasis by targeting the miR-186-5p/NGFR axis. Bioinformatics was used to analyse whether OIP5-AS1 targets miR-186-5p/NGFR and their expression characteristics in pancreatic cancer. OIP5-AS1 and NGFR were overexpressed in pancreatic cancer, and their levels showed a significant positive correlation. Clinical trials also demonstrated that high expression of OIP5-AS1 and NGFR and low expression of miR-186-5p played a pro-cancer role in pancreatic cancer. MiR-186-5p inhibited the migration and invasion of colon cancer cells by targeting NGFR-regulated p75NTR. OIP5-AS1 regulated the action of miR-186-5p on NGFR mRNA and p75NTR by targeting miR-186-5p. Downregulation of NGFR inhibited the expression of p75NTR protein and blocked the role of proNGF in promoting the migration and invasion of pancreatic cancer cells. Animal experiments also showed that the knockdown of miR-186-5p promoted cancer via the expression of NGFR mRNA and p75NTR protein, while the downregulation of proNGF blocked the effects. OIP5-AS1, as a ceRNA, promotes the progression of pancreatic cancer by targeting miR-186-5p/NGFR and affecting the prognosis of patients, which may be related to the action of proNGF.

HomeoboxC6 promotes metastasis by orchestrating the DKK1/Wnt/\u03b2-catenin axis in right-sided colon cancer

Patients with right-sided colon cancer (RCC) generally have a poorer prognosis than those with left-sided colon cancer (LCC). We previously found that homeobox C6 (HOXC6) was the most significantly upregulated gene in RCC compared to LCC. However, it remains unclear whether HOXC6 plays a role in tumor proliferation and metastasis. Our study aimed to explore the potential oncogenic role and the detailed molecular mechanism of HOXC6 in RCC. In this study, HOXC6 was validated to be overexpressed in RCC and associated with poor prognosis. Furthermore, overexpression of HOXC6 promoted the migration and invasion of colon cancer cells through inducing EMT by activating the Wnt/β-catenin signaling pathway and inhibition of DKK1 secretion. Lastly, we preliminary explored the translational effect of HOXC6 and found that silencing of HOXC6 made HCT116 and HT29 cells more sensitive to irinotecan.

Circular RNA SMARCA5 functions as an anti-tumor candidate in colon cancer by sponging microRNA-552

ABSTRACT It was reported that circular RNA (circRNA) circSMARCA5, as a tumor-related molecule, could modulate development of cancers, including prostatic cancer and cervical cancer. Nevertheless, the essential function of circSMARCA5 in colon cancer has not yet been confirmed. We aimed to investigate the role of circSMARCA5 in colon cancer. CircSMARCA5 expression in tumor cells was detected using RT-qPCR. CCK-8, colony formation, flow cytometry and Transwell assays evaluated the influences of circSMARCA5 in colon cancer cells. RT-qPCR, prediction database and luciferase report assay were accomplished for revealing the correlation between circSMARCA5 and miR-552. After transfection with miR-552 mimic, colon cancer cell behaviors were re-evaluated. Wnt and YAP1 pathways were explored by western blot. Our data presented that circSMARCA5 was under-expressed in colon cancer tissues. Transfection with overexpressing circSMARCA5 plasmid restrained growth, migration and invasion of colon cancer cells. Besides, circSMARCA5 directly sponged to miR-552 and miR-552 up-regulation offset the effects of circSMARCA5 on SW480 and SW620 cells. Furthermore, circSMARCA5 inactivated Wnt and YAP1 pathways by inhibiting miR-552. Anti-tumor role of sircSMARCA5 was showed in colon cancer cells as sponging miR-552 and blocking Wnt and YAP1 pathways.