lncRNA RP11-147L13.8 suppresses metastasis and chemo-resistance by modulating the phosphorylation of c-Jun protein in GBC

Bohao Zheng; Jiwen Wang; Kun Fan; Wentao Sun; Wenze Wan; Zhihui Gao; Xiaojian Ni; Dexiang Zhang; Xiaoling Ni; Tao Suo; Han Liu; Houbao Liu; Sheng Shen

doi:10.1016/j.omto.2021.08.016

lncRNA RP11-147L13.8 suppresses metastasis and chemo-resistance by modulating the phosphorylation of c-Jun protein in GBC

Mol Ther Oncolytics. 2021 Sep 3:23:124-137. doi: 10.1016/j.omto.2021.08.016. eCollection 2021 Dec 17.

Authors

Bohao Zheng^{1

2

3

4

5}, Jiwen Wang^{1

2

3

4

5}, Kun Fan^{1

2

3

4

5

6}, Wentao Sun^{1

2

3

4

5}, Wenze Wan^{1

2

3

4

5}, Zhihui Gao², Xiaojian Ni^{1

2

3

4

5}, Dexiang Zhang^{5

6}, Xiaoling Ni^{1

2

3

4

5}, Tao Suo^{1

2

3

4

5}, Han Liu^{1

2

3

4

5}, Houbao Liu^{1

2

3

4

5

6}, Sheng Shen^{1

2

3

4

5

6}

Affiliations

¹ Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China.
² Biliary Tract Disease Center of Zhongshan Hospital, Fudan University, Shanghai 200032, China.
³ Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
⁴ Biliary Tract Disease Institute, Fudan University, Shanghai 200032, China.
⁵ Shanghai Biliary Tract Minimal Invasive Surgery and Materials Engineering Research Center, Shanghai 200032, China.
⁶ Department of General Surgery, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai 200032, China.

Abstract

Long non-coding RNAs (lncRNAs) have been identified as critical contributors in tumor progression for many types of cancer. However, their functions in gallbladder cancer (GBC) have not been systematically clarified. In this study, the clinical significance, biological function, and underlying mechanism of lncRNA RP11-147L13.8 in GBC were investigated. The quantitative real-time PCR result indicated that lncRNA RP11-147L13.8 was found to be recurrently downregulated in GBC tumor samples. Kaplan-Meier analysis revealed that decreased lncRNA RP11-147L13.8 expression level was associated with poor survival of GBC patients (p = 0.025). Then, both in vitro and in vivo experiments elucidated that the overexpression of lncRNA RP11-147L13.8 suppressed the migration and invasion abilities of GBC cells and promoted the sensitivity to gemcitabine of GBC cells. Furthermore, we found that lncRNA RP11-147L13.8 physically interacted with c-Jun protein and decreased the phosphorylation on serine-73 (c-Jun-Ser73), which might cause the enhancement of the migration, invasion, and sensitivity to gemcitabine of GBC tumor cells. In conclusion, our study identified lncRNA RP11-147L13.8 as a promising prognostic indicator for patients with GBC, providing insights into the molecular pathogenesis of GBC. lncRNA RP11-147L13.8 is a potential therapeutic combination for gemcitabine in GBC treatment.

Keywords: c-Jun; chemo-resistance; gallbladder cancer; long non-coding RNAs; phosphorylation.