Expression of KLF6-SV2 in colorectal cancer and its impact on proliferation and apoptosis

Zhang, Biao; Guo, Dandan; Zheng, Jiaying; Wu, Yanan

doi:10.1097/cej.0000000000000410

Cited by 20 publications

(21 citation statements)

References 17 publications

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“…Early studies demonstrated that KLF6 is frequently inactivated in CRC [28]. A recent study revealed that the mRNA level of KLF-SV2 tended to be reduced in CRC tissues compared with that in adjacent non-tumor tissues [29]. Additionally, overexpression of KLF-SV2 markedly decreased the proliferation and enhanced the apoptotic rate of SW480 and SW620 cells.…”

Section: Discussionmentioning

confidence: 99%

Upregulated Long Noncoding RNA LINC01234 Predicts Unfavorable Prognosis for Colorectal Cancer and Negatively Correlates With KLF6 Expression

Jiang

Zhu

et al. 2020

Ann Lab Med

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Background: LINC01234, a long noncoding RNA (lncRNA), is overexpressed in several cancers, including colorectal cancer (CRC). We investigated the role of LINC01234 in CRC development and confirmed its correlation with Krüppel-like factor 6 (KLF6), a tumor suppressor gene that is dysregulated in CRC. Methods:We tested mRNA levels using quantitative reverse transcription PCR (qRT-PCR). Tissue samples from patients with CRC, inflammatory bowel disease (IBD), hyperplastic polyp, and adenoma were included. Correlations between clinicopathological parameters, overall survival (OS) rate, and LINC01234 were analyzed using Kruskal-Wallis H test. Additionally, cell proliferation, apoptosis, and tumor formation in nude mice were tested to investigate the mechanism of LINC01234. Western blotting was used to determine protein levels.Results: LINC01234 expression was significantly upregulated in CRC tissues and CRC cell lines than in non-tumor tissues and normal epithelial cells, respectively. LINC01234 was associated with high tumor stage, larger tumor size, and metastasis. Patients with higher LINC01234 expression showed reduced OS. Cell proliferation was inhibited by LINC01234 knockdown, whereas apoptosis was enhanced. Mice injected with SW480 cells with LINC01234 knockdown displayed decreased tumor volume, weight, and Ki-67 levels compared with those injected with control cells. KLF6 was negatively regulated by LINC01234. Overexpression of KLF6 showed effects similar to those observed following LINC01234 knockdown on cell proliferation and apoptosis.Conclusions: LINC01234 could be a prognostic biomarker in CRC patients. Upregulation of LINC01234 in CRC promotes tumor development through negative regulation of KLF6. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Section: Discussionmentioning

confidence: 99%

Upregulated Long Noncoding RNA LINC01234 Predicts Unfavorable Prognosis for Colorectal Cancer and Negatively Correlates With KLF6 Expression

Jiang

Zhu

et al. 2020

Ann Lab Med

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“…Moreover, they also found that KLF6-SV1 was significantly higher in young patients than in adult patients ( P =0.0003). Zhang et al 19 used qRT-PCR to detect wtKLF6, KLF6-SV1, KLF6-SV2 and KLF6-SV3 at the mRNA level in a total of 60 colorectal cancer (CRC) patients and found that the splice variants represented 1.5%–15.9% compared with wt KLF6, and SV1 mRNA expression was higher than SV2 and SV3 mRNA expression. The total, wild type, SV2 and SV3 of KLF6 were decreased except for SV1 expression increased in CRC samples.…”

Section: Discussionmentioning

confidence: 99%

KLF6-SV1 is a new prognostic biomarker in postoperative patients with non-small cell lung cancer

Zhang

et al. 2018

CMAR

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ObjectivesNon-small cell lung cancer (NSCLC) is aggressive and associated with a poor prognosis. Recent studies have revealed that several genes are involved in the origin and progression of NSCLC. Kruppel-like factor 6 (KLF6) inactivation has been shown in some malignant tumors. KLF6-SV1, as one of the alternatively spliced KLF6 isoforms, has been found to be correlated with metastatic potential and poor survival in some cancers. The purpose of this study was to investigate the clinical and prognostic significance of KLF6-SV1 expression in NSCLC patients after curative resection.Patients and methodsA total of 79 patients were enrolled in this study. Enumeration data were analyzed using the chi-squared test or Fisher’s exact probability test. Measurement data were represented as average±SD and t-test (homoscedasticity) or t’-test (homoscedasticity uneven). Univariate analysis was performed by modeling Kaplan–Meier survival curves. The log-rank test was used to calculate the survival rate. Multivariate analysis was carried out by the use of the Cox proportional hazard model.ResultsKLF6-SV1 expression was correlated with pN (P<0.05) and pTNM stage (P<0.05). The expression of KLF6-SV1 in the adenocarcinoma group was significantly higher than that in the squamous cell carcinoma group (P<0.05). The 5-year survival rate for 79 NSCLC patients was 40.5%, and it was significantly associated with differentiation (P<0.05), pN (P<0.01), pTNM stage (P<0.01) and high expression of KLF6-SV1 (P<0.01). Cox multivariate regression demonstrated that differentiation, pN and KLF6-SV1 expression were independent factors for the 5-year survival rate.ConclusionKLF6-SV1 expression in adenocarcinoma was significantly higher than that in the squamous cell carcinoma, and high expression of KLF6-SV1 was significantly associated with pN and pTNM stage and poor survival in NSCLC patients.

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“…Cell proliferation and apoptosis are regulated by multiple molecules and mechanisms that regulate the physiological or pathological growth of tissues and organs. The aberrant dynamic balance of cell proliferation and apoptosis leads to the occurrence of many diseases, such as polyps [ 19 , 20 ], precancerous lesions [ 21 ], and tumors [ 22 ]. In the present study, the finding that apoptosis and cell proliferation of cells derived from untreated nasal polyp tissue was increased has been supported by a previous study [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Erythromycin on the Proliferation and Apoptosis of Cultured Nasal Polyp-Derived Cells and the Extracellular Signal-Regulated Kinase (ERK)/Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway

et al. 2018

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BackgroundErythromycin and its derivatives have been used to treat nasal polyposis and reduce inflammation, but the mechanism of action remains unclear. The extracellular signal-regulated kinase (ERK) and mitogen-activated protein kinase (MAPK) pathway proteins are expressed in nasal polyps. The aim of this study was to investigate the effects of erythromycin on cell proliferation, apoptosis, and the expression of p-MEK1 and p-ERK1 on cultured nasal polyp-derived cells.Material/MethodsNasal polyp-derived cells (n=32) and control cells from normal inferior turbinate tissue (n=32) were divided into four groups: the control group; the erythromycin-treated (100 μM) group; the selumetinib-treated (2 nM) group; and the erythromycin + selumetinib-treated group. Western blot was used to detect p-MEK1 and p-ERK1 proteins. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect mRNA expression of BCL-2 and BAX. Flow cytometry detected expression of Ki-67 and cell apoptosis. Cell apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL). Spectrophotometry assessed caspase-3 activity.ResultsThe expression of Ki-67 was significantly increased, and cell apoptosis was significantly reduced in untreated nasal polyp-derived cells compared with controls. Erythromycin treatment significantly decreased cell proliferation and the expression of p-MEK1 and p-ERK1, and increased apoptosis in nasal polyp-derived cells compared with control cells. Selumetinib treatment had a synergistic effect with erythromycin to reduce the expression of p-MEK1 and p-ERK1, reduce cell proliferation, and increase cell apoptosis.ConclusionsIn cultured cells derived from nasal polyps, erythromycin treatment reduced cell proliferation and increased apoptosis by inhibiting the activation of the ERK/MAPK signaling pathway.

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Expression of KLF6-SV2 in colorectal cancer and its impact on proliferation and apoptosis

Abstract: Supplemental Digital Content is available in the text.

Cited by 20 publications

References 17 publications

Upregulated Long Noncoding RNA LINC01234 Predicts Unfavorable Prognosis for Colorectal Cancer and Negatively Correlates With KLF6 Expression

Upregulated Long Noncoding RNA LINC01234 Predicts Unfavorable Prognosis for Colorectal Cancer and Negatively Correlates With KLF6 Expression

KLF6-SV1 is a new prognostic biomarker in postoperative patients with non-small cell lung cancer

Effects of Erythromycin on the Proliferation and Apoptosis of Cultured Nasal Polyp-Derived Cells and the Extracellular Signal-Regulated Kinase (ERK)/Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway

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