Abstract

To explore the role of long-chain non-coding RNA (lncRNA) taurine up-regulated gene 1 (TUG1) in the development of colorectal cancer (CRC) via the miR-138-5p/zinc finger E-box-binding homeobox 2 (ZEB2) axis.Eighty-four CRC tissue specimens and 84 corresponding paracancerous tissue specimens were sampled from 84 patients with CRC admitted to the First Hospital of Jilin University from January 2018 to September 2019. The TUG1 expression in the specimens was determined, and its value in diagnosis and prognosis of CRC was analyzed. Additionally, constructed stable and transient overexpresison vectors and inhibition vectors were transfected into CRC cells. The MTT, transwell, and flow cytometry were adopted for analysis on the proliferation, invasion, and apoptosis of transfected cells, respectively, and a dual luciferase reporter (DLR) assay was carried out for correlation determination between TUG1 and miR-138-5p and between miR-138-5p and ZEB2.TUG1 was up-regulated in CRC, and serum TUG1 could be adopted as a diagnostic marker of CRC, with area-under-the-curve (AUC) larger than 0.8. In addition, siRNA-TUG1, shRNA-TUG1, miR-138-5p-mimics, and miR-138-5p-inhibitor were transfected into cells, and it turned out that overexpressing miR-138-5p and inhibiting ZEB2 exerted the same effects. The DLR assay revealed that TUG1 was able to targetedly regulate miR-138-5p, and miR-138-5p could targetedly regulate ZEB2, and in vitro experiments revealed that TUG1 could affect the epithelial-to-mesenchymal transition (EMT) of CRC via the miR-138-5p/ZEB2 axis.TUG1 could promote the development of CRC via the miR-138-5p/ZEB2 axis.

Highlights

  • Colorectal cancer (CRC) is the third most prevalent cancer in the globe, and one of the common digestive system malignant tumors in the gastrointestinal tract, which results in more than 1 million deaths every year [1,2]

  • One study has uncovered that knockdown of taurine up-regulated gene 1 (TUG1) via shRNA can inhibit the formation of renal cell carcinoma in vivo and in vitro through the miR-299-3p/VEGF axis [18], and one other study by Yang et al [19] has revealed that long-chain non-coding RNA (lncRNA) TUG1 participates in pulmonary vascular remodeling of hypoxic pulmonary hypertension mice through miR-374c-mediated Foxc1

  • Our study was to explore the effect of lncRNA TUG1 on the progression and biological function of CRC by regulating the miR-138-5p/zinc finger E-box-binding homeobox 2 (ZEB2) axis

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Summary

Introduction

Colorectal cancer (CRC) is the third most prevalent cancer in the globe, and one of the common digestive system malignant tumors in the gastrointestinal tract, which results in more than 1 million deaths every year [1,2]. Despite a great advancement in the treatment methods of CRC including surgery, chemotherapy, radiation, and combined therapy, the prognosis of CRC patients is still poor according to clinical data [4,5]. Molecular targeting takes an increasingly crucial part in the diagnosis, staging, and comprehensive treatment of CRC. Some studies have revealed that CRC development is linked to long-chain non-coding RNA (LncRNA), and a deeper understanding of the molecular mechanism of CRC can provide novel insights into the pathogenesis of the disease, increasing treatment options [6,7,8].

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