Cancer Management and Research (Sep 2019)

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

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

Journal volume & issue
Vol. Volume 11
pp. 8607 – 8617

Abstract

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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 workCorrespondence: Linyou ZhangDepartment of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, People’s Republic of ChinaEmail [email protected] ZhangDepartment 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 ChinaEmail [email protected]: 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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