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Effects of Long Non-Coding RNA RP11-468E2.5 on Cell Proliferation and Apoptosis in Colorectal Cancer Cells by Targeting STAT5 and STAT6 via the JAK/STAT Signaling Pathway
44 Pages Posted: 29 Mar 2019
More...Abstract
Background: Long noncoding RNAs (lncRNAs), as tumor-associated biological molecules, have been reported and studied in the progression of colorectal cancer (CRC). This study aims to examine the effects of lncRNA RP11-468E2.5 and its target genes: STAT5 and STAT6 on the biological activities of CRC cells via the JAK/STAT signaling pathway.
Methods: Differentially expressed lncRNAs related to CRC were initially screened from the GEO database. A Multi Experiment Matrix website was used to predict target genes. CRC tissues and adjacent normal tissues were then collected from 169 CRC patients. Human CRC HCT116 and SW480 cells were treated with siRNA against lncRNA RP11-468E2.5, AG490 (inhibitor of JAK/STAT signaling pathway), or AG490 + siRNA against lncRNA RP11-468E2.5. The effects of RP11-468E2.5 on cellular activities such as cell viability, cycle distribution and cell apoptosis were analyzed following the cell treatment. The relationship of RP11-468E2.5 to the JAK/STAT pathway was examined by RT-qPCR and western blot assay.
Findings: The CRC-related gene chip data showed that lncRNA RP11-468E2.5 was poorly expressed in CRC. Furthermore, RP11-468E2.5 was confirmed to target STAT5 and STAT6, which participated in the JAK/STAT signaling pathway. CRC tissues showed decreased expression of RP11-468E2.5 and increased expression of STAT5, STAT6 and Cyclin D1 (CCND1), when compared to that of adjacent normal tissues. The treatment of siRNA against lncRNA RP11-468E2.5 resulted in a significant increase of expression in JAK1, STAT3, STAT5, p-STAT3, p-STAT5, STAT6, p-STAT6, CCND1 and Bcl-2, as well as a significantly lower expression of P21 and P27. Comparatively, the opposite trend was observed when cells were treated with AG490. Furthermore, the treatment of siRNA against lncRNA RP11-468E2.5 produced increased CRC cell proliferation and reduced cell apoptosis along with promoted cell cycle entry. Meanwhile, the treatment of AG490 reversed the results.
Conclusions: It was concluded that the up-regulation of lncRNA RP11-468E2.5 inhibits the JAK/STAT signaling pathway by targeting STAT5 and STAT6, thereby suppressing cell proliferation and promoting cell apoptosis in CRC.
Funding Statement: The authors state: "None."
Declaration of Interests: The authors have declared that no competing interests exist.
Ethics Approval Statement: This study was performed with the approval from the Ethics Committee in Harbin Medical University Tumour Hospital. All participating patients provided written informed consents.
Keywords: Long noncoding RNA RP11-468E2.5; Colorectal cancer; STAT5 gene; STAT6 gene; Janus kinase-signal transducer and activator of transcription signaling pathway; Proliferation; Apoptosis
Suggested Citation: Suggested Citation