1. Academic Validation
  2. Long non-coding RNA RP11-197K6.1 as ceRNA promotes colorectal cancer progression via miR-135a-5p/DLX5 axis

Long non-coding RNA RP11-197K6.1 as ceRNA promotes colorectal cancer progression via miR-135a-5p/DLX5 axis

  • J Transl Med. 2024 May 17;22(1):469. doi: 10.1186/s12967-024-05286-5.
Mingkun Wang # 1 2 3 Xuben Niu # 4 2 3 Maihuan Wang 2 Peng Zheng 1 2 3 Xiaoya Liu 4 2 3 Zhen Cao 5 6 7 8 Chaojun Zhang 9 10 11
Affiliations

Affiliations

  • 1 The Fifth School of Clinical Medicine, Navy Clinical College, Anhui Medical University, Hefei, Anhui, 230032, China.
  • 2 Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing road, Haidian District, Beijing, 100853, China.
  • 3 Department of General Surgery, The Sixth Medical Center of PLA General Hospital, 6 Fucheng road, Haidian District, Beijing, 100048, China.
  • 4 Department of General Surgery, School of Medicine, South China University of Technology, Guangzhou, 510006, China.
  • 5 The Fifth School of Clinical Medicine, Navy Clinical College, Anhui Medical University, Hefei, Anhui, 230032, China. zhenyacy@163.com.
  • 6 Department of General Surgery, School of Medicine, South China University of Technology, Guangzhou, 510006, China. zhenyacy@163.com.
  • 7 Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing road, Haidian District, Beijing, 100853, China. zhenyacy@163.com.
  • 8 Department of General Surgery, The Sixth Medical Center of PLA General Hospital, 6 Fucheng road, Haidian District, Beijing, 100048, China. zhenyacy@163.com.
  • 9 The Fifth School of Clinical Medicine, Navy Clinical College, Anhui Medical University, Hefei, Anhui, 230032, China. zcjdlyxzx@163.com.
  • 10 Department of General Surgery, School of Medicine, South China University of Technology, Guangzhou, 510006, China. zcjdlyxzx@163.com.
  • 11 Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, 28 Fuxing road, Haidian District, Beijing, 100853, China. zcjdlyxzx@163.com.
  • # Contributed equally.
Abstract

Background: Colorectal Cancer (CRC) remains a major global health challenge, with high incidence and mortality rates. The role of long noncoding RNAs (lncRNAs) in Cancer progression has received considerable attention. The present study aimed to investigate the function and mechanisms underlying the role of lncRNA RP11-197K6.1, microRNA-135a-5p (hsa-miR-135a-5p), and DLX5 in CRC development.

Methods: We analyzed RNA Sequencing data from The Cancer Genome Atlas Colorectal Cancer dataset to identify the association between lncRNA RP11-197K6.1 and CRC progression. The expression levels of lncRNA RP11-197K6.1 and DLX5 in CRC samples and cell lines were determined by real-time quantitative PCR and western blotting assays. Fluorescence in situ hybridization was used to confirm the cellular localization of lncRNA RP11-197K6.1. Cell migration capabilities were assessed by Transwell and wound healing assays, and flow cytometry was performed to analyze Apoptosis. The interaction between lncRNA RP11-197K6.1 and miR-135a-5p and its effect on DLX5 expression were investigated by the dual-luciferase reporter assay. Additionally, a xenograft mouse model was used to study the in vivo effects of lncRNA RP11-197K6.1 on tumor growth, and an immunohistochemical assay was performed to assess DLX5 expression in tumor tissues.

Results: lncRNA RP11-197K6.1 was significantly upregulated in CRC tissues and cell lines as compared to that in normal tissues, and its expression was inversely correlated with patient survival. It promoted the migration and metastasis of CRC cells by interacting with miR-135a-5p, alleviated suppression of DLX5 expression, and facilitated tumor growth.

Conclusion: This study demonstrated the regulatory network and mechanism of action of the lncRNA RP11-197K6.1/miR-135a-5p/DLX5 axis in CRC development. These findings provided insights into the molecular pathology of CRC and suggested potential therapeutic targets for more effective treatment of patients with CRC.

Keywords

Colorectal cancer; DLX5; Long noncoding RNA; RP11-197K6.1; miR-135a-5p; miRNA.

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