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Downregulated MCOLN1 Attenuates The Progression Of Non-Small-Cell Lung Cancer By Inhibiting Lysosome-Autophagy

Authors Yin C, Zhang H, Liu X, Zhang H, Zhang Y, Bai X, Wang L, Li H, Li X, Zhang S, Zhang L, Zhang Y

Received 21 May 2019

Accepted for publication 6 September 2019

Published 23 September 2019 Volume 2019:11 Pages 8607—8617

DOI https://doi.org/10.2147/CMAR.S216538

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Nicola Ludin

Peer reviewer comments 2

Editor who approved publication: Dr Chien-Feng Li


Video abstract presented by Yin C.

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Chuntong Yin,1,* Han Zhang,1,* Xin Liu,2 Haiying Zhang,2 Yue Zhang,2 Xue Bai,2 Lei Wang,2 Huimin Li,2 Xia Li,2 Shuqian Zhang,2 Linyou Zhang,1 Yong Zhang2

1Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, People’s Republic of China; 2Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Linyou Zhang
Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, People’s Republic of China
Email hmulyzhang@outlook.com
Yong Zhang
Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, People’s Republic of China
Email hmuzhangyong@hotmail.com

Objectives: Autophagy plays various roles in non-small-cell lung cancer (NSCLC). MCOLN1, a reactive oxygen species sensor, can regulate autophagy via lysosomal Ca(2+); however, the role of MCOLN1 in NSCLC is largely unknown. This study aimed to explore the effects of MCOLN1 on proliferation, invasion and migration in NSCLC and the underling mechanisms.
Materials and methods: The tissues of NSCLC patients were collected, then MCOLN1 expression in tumor and adjacent tissues was measured and its relationship with pathological staging was analyzed. The Cell Counting Kit-8 (CCK-8) assay, wound healing assay and transwell migration assay were used to evaluate the proliferation, migration and invasion ability, respectively. Live-cell imaging and transmission electron microscopy (TEM) were used to observe autophagic flux and autolysosomes.
Results: It was found that MCOLN1 expression was significantly decreased in human NSCLC tissues compared with normal lung tissues while more MCOLN1 in stage III–IV was shown than stage I–II, indicating that MCOLN1 increased along with the progression of NSCLC. Furthermore, CCK-8 assay, wound healing assay and transwell migration assay confirmed that the inhibition of MCOLN1 suppressed NSCLC cells proliferation migration and invasion. Overexpression of MCOLN1 promoted autophagy in A549 and H1299 cells with increased LC3-II/I, lamp1 expression and autolysosomes as well as autophagic flux shown by live-cell imaging and TEM.
Conclusion: Our study shows that downregulated MCOLN1 reduced lysosome-autophagy activity contributing to inhibited tumor progression, which reveals a novel role of MCOLN1 in NSCLC, and targeting MCOLN1 may be a therapeutic potential for NSCLC.

Keywords: MCOLN1, NSCLC, autophagy, lysosome, progression

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