Long non‑coding RNA CASC2 suppresses pancreatic cancer cell growth and progression by regulating the miR‑24/MUC6 axis

Xu,Da‑Fang; Wang,Li‑Shan; Zhou,Jia‑Hua

doi:10.3892/ijo.2019.4937

Long non‑coding RNA CASC2 suppresses pancreatic cancer cell growth and progression by regulating the miR‑24/MUC6 axis

Authors:
- Da‑Fang Xu
- Li‑Shan Wang
- Jia‑Hua Zhou
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Affiliations: Department of Hepatic‑Biliary‑Pancreatic Center, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
Published online on: December 10, 2019 https://doi.org/10.3892/ijo.2019.4937
Pages: 494-507
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Recent evidence indicates that the long non‑coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) is involved in tumorigenesis of several types of cancer through targeting microRNAs (miRs); however, the molecular mechanism of CASC2 in pancreatic cancer remains elusive. In the present study, the expression levels of CASC2, miR‑24 and mucin 6 (MUC6) were measured in pancreatic cancer specimens and cell lines by reverse transcription‑quantitative PCR. Western blotting was used to determine the protein expression levels of MUC6, Integrin β4 (ITGB4), phosphorylated (p)‑focal adhesion kinase (FAK) and several epithelial‑to‑mesenchymal transition markers in pancreatic cancer cells. MTT, colony formation, wound healing, Transwell and flow cytometry assays were performed to detect cell proliferation, colony formation, migration, invasion and apoptosis, respectively, in vitro. Morphological changes of pancreatic cancer cells were assessed by light microscopy. The interactions between CASC2, miR‑24 and MUC6 were assessed by the dual‑luciferase reporter assay. A tumor xenograft model was generated to investigate tumor growth in vivo. CASC2 and MUC6 were downregulated, and miR‑24 was upregulated in pancreatic cancer specimens and cell lines. Functionally, CASC2 overexpression or miR‑24 knockdown suppressed pancreatic cancer cell proliferation, colony formation, migration and invasion, and promoted apoptosis. Additionally, they altered cell‑cell adhesion as demonstrated by the attenuated ITGB4, p‑FAK and N‑cadherin protein levels, as well as morphological changes. Mechanistically, CASC2 sponged miR‑24 and activated its downstream target MUC6 to suppress pancreatic cancer growth and progression. CASC2 exerted tumor‑suppressive functions in pancreatic cancer through the miR‑24/MUC6 axis, which may be a promising target for pancreatic cancer therapy.

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