Long non-coding RNA CCAL regulates colorectal cancer progression by activating Wnt/β-catenin signalling pathway via suppression of activator protein 2α.
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.
['Ma|Yanlei|Y|', 'Yang|Yongzhi|Y|', 'Wang|Feng|F|', 'Moyer|Mary-Pat|MP|', 'Wei|Qing|Q|', 'Zhang|Peng|P|', 'Yang|Zhe|Z|', 'Liu|Weijie|W|', 'Zhang|Huizhen|H|', 'Chen|Niwei|N|', 'Wang|Hua|H|', 'Wang|Huamin|H|', 'Qin|Huanlong|H|']
D000236:Adenoma D063646:Carcinogenesis D002277:Carcinoma D015179:Colorectal Neoplasms D018450:Disease Progression D015972:Gene Expression Regulation, Neoplastic D006801:Humans D009367:Neoplasm Staging D062085:RNA, Long Noncoding D050656:Transcription Factor AP-2 D060449:Wnt Signaling Pathway
COLORECTAL CANCER