Abstract

BackgroundThe abnormal expression of many long non-coding RNAs (lncRNAs) has been reported in the progression of various tumors. However, the potential biological roles and regulatory mechanisms of long non-coding RNAs in the development of colorectal cancer (CRC) have not yet been fully elucidated. Therefore, it is crucial to identify that lncRNAs can be used for the clinical prevention and treatment of CRC.MethodsIn our previous work, we identificated a novel lncRNA, lncRNA-KAT7, and found that the expression of lncRNA-KAT7 in CRC tissues was significantly lower than that in matched normal intestinal tissues, and the expression in CRC cell lines was lower than that of normal intestinal epithelial cells (P < 0.05). Besides, the expression of lncRNA-KAT7 is negative associated with age, tumor size, tumor differentiation, lymph node metastasis of CRC patients. The potential biological effects and molecular mechanisms of lncRNA-KAT7 in CRC were evaluated using a series of CCK-8 assay, clone formation assay, EdU proliferation assay, scratch determination, transwell determination, western blot analysis, and nude subcutaneous tumorigenesis model construction cell and animal experiments.ResultsThe expression of lncRNA-KAT7 in CRC tissues was lower than that in matched normal tissues and normal intestinal epithelial cells (P < 0.05). Decreased expression of lncRNA-KAT7 is associated with clinicopathological features of poor CRC patients. In vitro experiments showed that up-regulation of lncRNA-KAT7 expression in CRC cells inhibited cell proliferation and migration. In vivo animal experiments showed that the lncRNA-KAT7 also inhibited tumor growth. Western blot analysis showed that the expression of lncRNA-KAT7 was up-regulated in HCT116 cells, the expression of E-cadherin increased, and the expression of Vimentin, MMP-2 and β-catenin protein was down-regulated so did the phosphorylation NF-κB P65. The results confirm that the expression of lncRAN-KAT7 can inhibit the malignant phenotype of CRC cells.ConclusionsUp to now, as a novel lncRNA, lncRNA-KAT7 has not any relevant research and reports. The results confirm that the expression of lncRNA-KAT7 can inhibit the malignant phenotype of CRC cells. And it can be used as a new diagnostic biomarker and therapeutic target for the development of CRC.

Highlights

  • The abnormal expression of many long non-coding RNAs has been reported in the progression of various tumors

  • LncRNA‐KAT7 is low expressed in colorectal cancer (CRC) tissues The relative expression levels of long non-coding RNAs (lncRNAs)-KAT7 were measured using qRT-PCR in 140 patients with CRC, normalized to GAPDH

  • LncRNA-KAT7 was down-regulated in 71.4% (100/140) of CRC tissues compared with matched adjacent normal tissues (P < 0.05, Fig. 1d, e)

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Summary

Introduction

The abnormal expression of many long non-coding RNAs (lncRNAs) has been reported in the progression of various tumors. The potential biological roles and regulatory mechanisms of long non-coding RNAs in the development of colorectal cancer (CRC) have not yet been fully elucidated. The incidence of CRC is on the rise, showing a trend of younger age. It is still the focus of global health concerns [2]. The mortality rate for patients with CRC metastasis remains high, and metastasis is still one of the key factors causing low clinical efficacy, poor survival period, and poor prognosis in CRC patients [5]. The prevalence and poor outcome of CRC prompted us to reveal the pathological mechanism of CRC progression and to find effective biomarkers for diagnosis and prognosis

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