Background

Pancreatic cancer is a fatal malignancy with a poor prognosis worldwide [1]. Due to occult onset and non-specific symptoms, 80% of patients diagnosed with pancreatic cancer are in advanced stages and have a 5-year survival rate of less than 5% [2, 3]. Despite ongoing advances for the survival rates noted in many cancers, such as colon cancer and breast cancer, the annual mortality rates for patients with pancreatic cancer remain almost equal to the incidence rates [3, 4]. Thus, to improve the health outcomes of pancreatic cancer patients, more intensive efforts should be made to understand the molecular mechanisms underlying pancreatic cancer progression.

Anillin (ANLN), an actin binding protein, first identified in Drosophila, is located on chromosome 7p14.2 and encodes an actin-binding protein that consists of 1125 amino acids and plays an important role in cytokinesis [5,6,7]. In normal tissues, ANLN expression is higher in the placenta, brain and testis, and lower in the lung, heart, liver and spleen [8]. Many recent studies suggests that ANLN is upregulated in numerous cancer types, including cervical cancer, prostate cancer, anaplastic thyroid carcinoma, breast cancer, lung carcinogenesis, bladder urothelial carcinoma, pancreatic cancer and nasopharyngeal carcinoma [9,10,11,12,13,14,

Availability of data and materials

All data generated or analyzed during this study are included in this published article and its additional files.

Abbreviations

ANLN:

Anillin actin binding protein

CCK-8:

Cell counting kit-8

EZH2:

Enhancer of zeste homolog 2

GO:

Gene ontology

IHC:

Immunohistochemistry

LASP1:

LIM and SH3 protein 1

MOI:

Multiplicity of infection

OS:

Overall survival

qRT-PCR:

Quantitative reverse transcription polymerase chain reaction

shRNA:

Short hairpin RNA

siRNA:

Small interfering RNA

UTR:

Untranslated region

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Acknowledgements

Not applicable.

Funding

This study was supported by the National Natural Science Foundation of China (no. 81472288 and no. 81472775).

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Author notes

  1. Anbin Wang and Haisu Dai contributed equally to this work.

Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China

    Anbin Wang, Haisu Dai, Yi Gong, Chengcheng Zhang, Junjie Shu, Yuandeng Luo, Yan Jiang, Wei Liu & ** Bie

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Contributions

ABW, HSD, WL and PB designed the experiments; ABW and HSD performed the experiments and analyzed the data; YG, CCZ, JJS, YDL and YJ collected and analyzed the clinical samples; ABW and HSD drafted the manuscript; WL and PB reviewed the manuscript. All authors have read and approved the final manuscript.

Corresponding authors

Correspondence to Wei Liu or ** Bie.

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This study was approved by the Ethical Committee of Army Medical University, China. All patients provided written informed consent to participate in the study.

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The authors declare that they have no competing interests.

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Additional files

Additional file 1:

Table S1. siRNAs, shRNA and primers. (DOCX 20 kb)

Additional file 2:

Table S2. GO terms representing biological process. (DOCX 17 kb)

Additional file 3:

Table S3. GO terms representing molecular function. (DOCX 17 kb)

Additional file 4:

Table S4. GO terms representing cellular compartment. (DOCX 19 kb)

Additional file 5:

Figure S1. ANLN knockdown inhibited BxPC-3 cell proliferation by mediating LASP1. (A) Based on the GENT database, LASP1, RAB11B, RUVBL1 and MYO1B gene expression were analyzed in the pancreatic cancer tissues and normal pancreatic tissues. (B) There were significant Pearson correlations of ANLN with LASP1 and ANLN with RUVBL1 in the pancreatic cancer tissues and the normal pancreatic tissues. (C) CCK-8 assay showed that LASP1 restoration partially reversed the effects of ANLN knockdown on pancreatic cancer cell proliferation, while RUVBL1 restoration did not reverse the effect of ANLN downregulation on pancreatic cancer cell proliferation. **P < 0.01. (JPG 1806 kb)

Additional file 6:

Figure S2. MiR-218-5p upregulation significantly repressed the expression of LASP1 mRNA in BxPC-3. (A) The heat map of the differentially expressed miRNA precursors with a fold change of greater than 2 or less than − 2 in ANLN RNAi relative to NC. (B) The selected candidate miRNAs (miR-145-5p, miR-218-5p and miR-9-5p) were confirmed by qRT-PCR after ANLN RNAi transfection in BxPC-3 cells. (C) The expression levels of miR-145-5p, miR-218-5p and miR-9-5p were detected by qRT-PCR in BxPC-3 cells transfected with the miR-145-5p mimic (miR-145-5p), miR-218-5p mimic (miR-218-5p), miR-9-5p mimic (miR-9-5p) or mimic control (con). U6 was used as a loading control. (D) The expression levels of LASP1 mRNA in BxPC-3 cells transfected with the miR-145-5p mimic (miR-145-5p), miR-218-5p mimic (miR-218-5p), miR-9-5p mimic (miR-9-5p) or mimic control (con) were analyzed by qRT-PCR. **P < 0.01. (JPG 1590 kb)

Additional file 7:

Figure S3. ANLN depletion significantly repressed the expression of EZH2 mRNA and protein in BxPC-3 and SW1990 cells. (A) The heat map of the selected genes. (B and C) The expression of EZH2 mRNA and protein was determined by qRT-PCR and Western blot in BxPC-3 and SW1990 cells transfected with the ANLN siRNA (ANLN RNAi) or the scramble control (NC). (JPG 512 kb)

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Wang, A., Dai, H., Gong, Y. et al. ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis. J Exp Clin Cancer Res 38, 347 (2019). https://doi.org/10.1186/s13046-019-1340-7

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