Positive feedback between lncRNA FLVCR1-AS1 and KLF10 may inhibit pancreatic cancer progression via the PTEN/AKT pathway

Jiewei Lin; Shuyu Zhai; Siyi Zou; Zhiwei Xu; Jun Zhang; Lingxi Jiang; Xiaxing Deng; Hao Chen; Chenghong Peng; Jiaqiang Zhang; Baiyong Shen

doi:10.1186/s13046-021-02097-0

Positive feedback between lncRNA FLVCR1-AS1 and KLF10 may inhibit pancreatic cancer progression via the PTEN/AKT pathway

J Exp Clin Cancer Res. 2021 Oct 11;40(1):316. doi: 10.1186/s13046-021-02097-0.

Authors

Jiewei Lin^#^{1

2

3

4}, Shuyu Zhai^#^{1

2

3

4}, Siyi Zou^#^{1

2

3

4}, Zhiwei Xu^{1

2

3

4}, Jun Zhang^{1

2

3

4}, Lingxi Jiang^{1

2

3

4}, Xiaxing Deng^{1

2

3

4}, Hao Chen^{1

2

3

4}, Chenghong Peng^{5

6

7

8}, Jiaqiang Zhang^{9

10

11

12}, Baiyong Shen^{13

14

15

16}

Affiliations

¹ Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ State Key Laboratory of Oncogenes and Related Genes, Shanghai, China.
⁴ Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁵ Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. chhpeng@188.com.
⁶ Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China. chhpeng@188.com.
⁷ State Key Laboratory of Oncogenes and Related Genes, Shanghai, China. chhpeng@188.com.
⁸ Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China. chhpeng@188.com.
⁹ Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. zjq12570@rjh.com.cn.
¹⁰ Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China. zjq12570@rjh.com.cn.
¹¹ State Key Laboratory of Oncogenes and Related Genes, Shanghai, China. zjq12570@rjh.com.cn.
¹² Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China. zjq12570@rjh.com.cn.
¹³ Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. shenby@shsmu.edu.cn.
¹⁴ Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China. shenby@shsmu.edu.cn.
¹⁵ State Key Laboratory of Oncogenes and Related Genes, Shanghai, China. shenby@shsmu.edu.cn.
¹⁶ Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China. shenby@shsmu.edu.cn.

^# Contributed equally.

Abstract

Background: FLVCR1-AS1 is a key regulator of cancer progression. However, the biological functions and underlying molecular mechanisms of pancreatic cancer (PC) remain unknown.

Methods: FLVCR1-AS1 expression levels in 77 PC tissues and matched non-tumor tissues were analyzed by qRT-PCR. Moreover, the role of FLVCR1-AS1 in PC cell proliferation, cell cycle, and migration was verified via functional in vitro and in vivo experiments. Further, the potential competitive endogenous RNA (ceRNA) network between FLVCR1-AS1 and KLF10, as well as FLVCR1-AS1 transcription levels, were investigated.

Results: FLVCR1-AS1 expression was low in both PC tissues and PC cell lines, and FLVCR1-AS1 downregulation was associated with a worse prognosis in patients with PC. Functional experiments demonstrated that FLVCR1-AS1 overexpression significantly suppressed PC cell proliferation, cell cycle, and migration both in vitro and in vivo. Mechanistic investigations revealed that FLVCR1-AS1 acts as a ceRNA to sequester miR-513c-5p or miR-514b-5p from the sponging KLF10 mRNA, thereby relieving their suppressive effects on KLF10 expression. Additionally, FLVCR1-AS1 was shown to be a direct transcriptional target of KLF10.

Conclusions: Our research suggests that FLVCR1-AS1 plays a tumor-suppressive role in PC by inhibiting proliferation, cell cycle, and migration through a positive feedback loop with KLF10, thereby providing a novel therapeutic strategy for PC treatment.

Keywords: FLVCR1-AS1; KLF10; Pancreatic cancer; ceRNA; lncRNA.

MeSH terms

Animals
Cell Line, Tumor
Disease Progression
Early Growth Response Transcription Factors / metabolism*
Female
Heterografts
Humans
Kruppel-Like Transcription Factors / metabolism*
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Middle Aged
PTEN Phosphohydrolase / metabolism*
Pancreatic Neoplasms / genetics
Pancreatic Neoplasms / metabolism*
Pancreatic Neoplasms / pathology
Proto-Oncogene Proteins c-akt / metabolism*
RNA, Long Noncoding / metabolism*

Substances

Early Growth Response Transcription Factors
KLF10 protein, human
Kruppel-Like Transcription Factors
RNA, Long Noncoding
Proto-Oncogene Proteins c-akt
PTEN Phosphohydrolase
PTEN protein, human

Grants and funding

#81802369/National Natural Science Foundation of China