LncRNA-ATB mediated E-cadherin repression promotes the progression of colon cancer and predicts poor prognosis.
BACKGROUND
Long non-coding RNA-activated by TGF-β (lncRNA-ATB) promotes the invasion-metastasis cascade in hepatocellular carcinoma via downregulating E-cadherin (E-cad) and inducing epithelial-to- mesenchymal transition (EMT) and is clinically significant in human colon cancer. However, its molecular mechanisms in colon cancer progression remain unclear. This study aimed to elucidate the role of lncRNA-ATB and its clinical value in colon cancer.


METHODS
Expression levels of lncRNA-ATB in colon cancer tissues and colon cancer cell lines were evaluated using quantitative real-time polymerase chain reaction. The clinicopathological significance and prognostic value of lncRNA-ATB were investigated, and roles of lncRNA-ATB in regulating E-cad and other EMT-related markers expression and colon cancer progression were evaluated in vitro. Expression levels of lncRNA-ATB and E-cad in human plasma were evaluated.


RESULTS
Long non-coding RNA-activated by TGF-β was upregulated in colon cancer tissues compared with adjacent mucosa (P < 0.001). LncRNA-ATB levels were also higher in metastatic cancer tissues (P < 0.001). Among the three highly invasive colon cancer cell lines, lncRNA-ATB levels were relatively higher with concurrent low levels of E-cad compared with levels in the three low-invasive cell lines. LncRNA-ATB expression correlated with pN stage (P < 0.01) and American Joint Committee on Cancer stage (P < 0.01). Striking differences were observed in overall survival and disease-free survival in cases with both high lncRNA-ATB expression and low E-cad expression. Reduction of lncRNA-ATB increased expression of epithelial markers E-cad, ZO-1, and decreased expression of mesenchymal markers ZEB1 and N-cadherin (N-cad), and significantly influenced colon cancer cell progression. Plasma lncRNA-ATB was upregulated in colon cancer patients one month after surgery (P < 0.05).


CONCLUSIONS
Long non-coding RNA-activated by TGF-β may act on colon tumorigenesis by suppressing E-cad expression and promoting EMT process, and lncRNA-ATB inhibition may provide a promising therapeutic option for suppressing colon cancer progression.
Department of General Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China.
Ben
B
Yue
Department of General Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China.
Shenglong
S
Qiu
Department of General Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China.
Senlin
S
Zhao
Department of General Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China.
Chenchen
C
Liu
Department of General Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China.
Dongyuan
D
Zhang
Department of General Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China.
Fudong
F
Yu
Department of General Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China.
Zhihai
Z
Peng
Department of General Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China.
Dongwang
D
Yan
D015820:Cadherins / Q000235:genetics* / Q000378:metabolism*; D063646:Carcinogenesis / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000378:metabolism / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation
D015820:Cadherins; D062085:RNA, Long Noncoding; D016212:Transforming Growth Factor beta
E-cadherin; TGF-β; colon cancer; lncRNA-ATB; oncogene