HSPB8 promoted intrahepatic cholangiocarcinoma progression by enhancing epithelial-mesenchymal transition and autophagy

Bo Shu; Yingxia Zhou; Qingchun Liang; Chao He; Fazhao Li

doi:10.1016/j.yexmp.2021.104691

HSPB8 promoted intrahepatic cholangiocarcinoma progression by enhancing epithelial-mesenchymal transition and autophagy

Exp Mol Pathol. 2021 Dec:123:104691. doi: 10.1016/j.yexmp.2021.104691. Epub 2021 Oct 1.

Authors

Bo Shu¹, Yingxia Zhou², Qingchun Liang³, Chao He⁴, Fazhao Li⁵

Affiliations

¹ Attending Physician of General Surgery, Second Xiangya Hospital of Central South University, No. 139 Renmin Middle Road, Changsha, Hunan Province, China.
² Nurse of Operation, Department of Xiangya Second Hospital of Central South University, No. 139 Renmin Middle Road, Changsha, Hunan Province, China.
³ Department of Pathology, Second Xiangya Hospital, Central South University, No. 139 Renmin Middle Road, Changsha, Hunan Province, China.
⁴ Department of General Surgery, Second Xiangya Hospital, Central South University, No. 139 Renmin Middle Road, Changsha, Hunan Province, China.
⁵ Chief Physician, Department of Liver Surgery, Second Xiangya Hospital, Central South University, No. 139 Renmin Middle Road, Changsha, Hunan Province, China. Electronic address: Fazhaoli@csu.edu.cn.

PMID: 34606781
DOI: 10.1016/j.yexmp.2021.104691

Abstract

Purpose: Heat shock protein B8 (HSPB8) has been recently discovered to be participated in the regulation of tumor progression. However, the function of HSPB8 in intrahepatic cholangiocarcinoma (ICC) has not yet been elucidated. This study studied the function of HSPB8 in ICC progression.

Methods: ICC patients (n = 150) were enrolled. The relationship between clinicopathological characteristics and HSPB8 expression was analyzed. RBE cells were transfected and treated by 3-MA. The RBE cells morphology was observed under a transmission electron microscope. Cell counting kit-8 assay, wound healing assay and Transwell experiment was conducted to detect RBE cells proliferation, migration and invasion. Quantitative reverse transcription-polymerase chain reaction, immunohistochemistry, Western blot and immunofluorescence were used for genes detection in clinical tissues and RBE cells.

Results: HSPB8 was up-regulated in ICC tissues than that in adjacent normal tissues. High HSPB8 expression in ICC indicated poor prognosis of patients. HSPB8 expression was mainly expressed in cell cytoplasm and aberrantly increased in RBE cells (P < 0.01). HSPB8 up-regulation promoted RBE cells proliferation, migration and invasion (P < 0.05). HSPB8 down-regulation reduced RBE cells proliferation, migration and invasion (P < 0.01). HSPB8 overexpression facilitated Vimentin expression, LC3-II/LC3-I ratio and inhibited E-cadherin, p62 expression in RBE cells (P < 0.05). Treatment of 3-MA partially reversed HSPB8 promotion on RBE cells proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) (P < 0.05 or P < 0.01).

Conclusion: HSPB8 promoted ICC progression by enhancing EMT and autophagy. HSPB8 might be an effective target for ICC treatment.

Keywords: Autophagy; EMT; HSPB8; ICC; Progression.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Autophagy / genetics*
Cadherins / genetics*
Cell Line, Tumor
Cell Movement / genetics
Cell Proliferation / genetics
Cholangiocarcinoma / genetics*
Cholangiocarcinoma / pathology
Epithelial-Mesenchymal Transition / genetics
Female
Gene Expression Regulation, Neoplastic / genetics
Heat-Shock Proteins / genetics*
Humans
Male
Microtubule-Associated Proteins / genetics
Middle Aged
Molecular Chaperones / genetics*
RNA-Binding Proteins / genetics

Substances

Cadherins
HSPB8 protein, human
Heat-Shock Proteins
MAP1LC3A protein, human
MAP1LC3B protein, human
Microtubule-Associated Proteins
Molecular Chaperones
P62 protein, human
RNA-Binding Proteins