|Table of Contents|

Mechanism of miR-506 inhibiting EMT of alitinib-resistant non-small cell lung cancer A549 cells by regulating MCL-1

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2021 02
Page:
190-195
Research Field:
Publishing date:

Info

Title:
Mechanism of miR-506 inhibiting EMT of alitinib-resistant non-small cell lung cancer A549 cells by regulating MCL-1
Author(s):
ZHONG Youqing1; ZHOU Xiangdong1; 2; LI Qi1; 2; QIN Yingjiao1
1.Department of Respiratory Medicine,the First Affiliated Hospital of Hainan Medical College，Hainan Haikou 570102,China;2.Key Laboratory of Emergency and Trauma,Ministry of Education of Hainan Medical University,Hainan Haikou 571199,China.
Keywords:
miR-506; apoptosis pathway of BAX/Bcl-2/MCL-1; non-small cell lung cancer; epithelial mesenchymal transformation (EMT); mechanism research
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2021.02.003
Abstract:
Objective:To investigate the effect and mechanism of miR-506 on the EMT and invasion and metastasis of alitinib-resistant non-small cell lung cancer A549 cells by regulating MCL-1.Methods:The cancer and adjacent tissues and A549 cells of human non-small cell lung cancer (NSCLC) were collected from 74 patients with non-small cell lung cancer who were confirmed to be resistant to aritinib by PET-CT combined with histopathological biopsy and drug sensitivity test admitted to the department of oncology of our hospital from December 2017 to December 2018.Cell transfection,immunohistochemical staining (IHC),qRT-PCR and Western Blot were used to detect the apoptosis pathways of miR-506,MCL-1,BAX/Bcl-2 and the expression levels of EMT marker proteins in clinical tissues and cell samples.In addition,Transwell cell assay was used to observe the effects of miR-506 overexpression and MCL-1 knockdown on migration and invasion ability of A549 cells.Results:The results of immunohistochemistry(IHC) showed that the invasive necrotizing pathological injury of the lung cancer patients was significantly worse than that of the adjacent tissues,and the positive expression rate of MCL-1 in the cancer tissues was 94.64%,which was significantly higher than the 23.27% of the adjacent tissues (P＜0.05).The results of qRT-PCR and Western Blot showed that the expressions of miR-506,BAX and E-cadherin in lung cancer tissues were significantly lower than those in adjacent positive tissues,while the expressions of MCL-1,Bcl-2 and N-cadherin were significantly higher than those in adjacent tissues (P＜0.05).Cell experiments showed that miR-506 overexpression and MCL-1 knockdown significantly up-regulated the expression of BAX and E-cadherin,and inhibited the expression of Bcl-2 and N-cadherin (P＜0.05).In addition,both miR-506 overexpression and MCL-1 knockdown significantly inhibited the migration and invasion of lung cancer A549 cells (P＜0.05).Conclusion:miR-506 may plays a crucial role in inhibiting EMT of A549 cells of alitinib-resistant non-small cell lung cancer and inducing apoptosis by inhibiting BAX/Bcl-2/MCL-1 apoptosis pathway,which is expected to provide new molecules and targets for clinical targeted therapies against lung cancer metastasis and apoptosis inhibition.

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Memo

Memo:
National Natural Science Foundation of China(No.81660010,8201153049）；国家自然科学资金项目（编号：81660010,8201153049）；海南省自然科学基金（编号：818MS147）
Last Update: 1900-01-01