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Long non-coding RNA CCAL regulates colorectal cancer progression by activating Wnt/β-catenin signalling pathway via suppression of activator protein 2α
  1. Yanlei Ma1,2,
  2. Yongzhi Yang1,
  3. Feng Wang1,2,
  4. Mary-Pat Moyer3,
  5. Qing Wei4,
  6. Peng Zhang1,
  7. Zhe Yang5,
  8. Weijie Liu5,
  9. Huizhen Zhang6,
  10. Niwei Chen7,
  11. Hua Wang8,
  12. Huamin Wang2,
  13. Huanlong Qin1
  1. 1Department of GI Surgery, Shanghai Tenth People's Hospital Affiliated with Tongji University, Shanghai, P. R. China
  2. 2Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
  3. 3INCELL Corporation, San Antonio, Texas, USA
  4. 4Departments of Pathology, Shanghai Tenth People's Hospital Affiliated with Tongji University, Shanghai, P. R. China
  5. 5Department of Surgery, The Sixth People's Hospital Affiliated with Shanghai Jiao Tong University, Shanghai, P. R. China
  6. 6Department of Pathology, The Sixth People's Hospital Affiliated with Shanghai Jiao Tong University, Shanghai, P. R. China
  7. 7Department of Digestive Endoscopy, The Sixth People's Hospital Affiliated with Shanghai Jiao Tong University, Shanghai, P. R. China
  8. 8Departments of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
  1. Correspondence to Dr Huanlong Qin, Department of GI Surgery, Shanghai Tenth People's Hospital Affiliated with Tongji University, 301 Yanchang Road, Shanghai 200072, P. R. China; hl-qin{at}hotmail.com or Dr. Huamin Wang, Department of Pathology, Unit 085, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA; hmwang{at}mdanderson.org

Abstract

Objective Long non-coding RNAs (lncRNAs) are emerging as key molecules in cancers, yet their potential molecular mechanisms are not well understood. The objective of this study is to examine the expression and functions of lncRNAs in the development of colorectal cancer (CRC).

Methods LncRNA expression profiling of CRC, adenoma and normal colorectal tissues was performed to identify tumour-related lncRNAs involved in colorectal malignant transformation. Then, we used quantitative reverse transcription PCR assays to measure the tumour-related lncRNA and to assess its association with survival and response to adjuvant chemotherapy in 252 patients with CRC. The mechanisms of CCAL function and regulation in CRC were examined using molecular biological methods.

Results We identified colorectal cancer-associated lncRNA (CCAL) as a key regulator of CRC progression. Patients whose tumours had high CCAL expression had a shorter overall survival and a worse response to adjuvant chemotherapy than patients whose tumours had low CCAL expression. CCAL promoted CRC progression by targeting activator protein 2α (AP-2α), which in turn activated Wnt/β-catenin pathway. CCAL induced multidrug resistance (MDR) through activating Wnt/β-catenin signalling by suppressing AP-2α and further upregulating MDR1/P-gp expression. In addition, we found that histone H3 methylation and deacetylases contributed to the upregulation of CCAL in CRC.

Conclusions Our results suggest that CCAL is a crucial oncogenic regulator involved in CRC tumorigenesis and progression.

  • COLORECTAL CANCER

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