Expression of autophagy-related proteins and genes in patients with non-small cell lung cancer_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

SUN Yuqing ¹ , CHENG Pengpeng ¹ , YU Haiyang ¹ , WANG Mengmeng ¹ , GUAN Wenbin ² ,  HAN Fengfeng ¹

1. Department of Respiratory Medicine, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P. R. China;
2. Department of Pathology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P. R. China;

Corresponding author：

HAN Fengfeng, Email: fengfh86@sina.com

Keywords：

Non-small cell lung cancer; Autophagy

DOI：

10.7507/1671-6205.201811038

Video：

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Objective To investigate the expression of autophagy-related genes and proteins in the lung tissues of patients with non-small cell lung cancer (NSCLC).Methods Pulmonary tissues were obtained from the surgically resected lung tissues of patients with NSCLC who were clinical diagnosed. The lung cancer tissues were derived from the pathologically diagnosed NSCLC and the normal tissues were from lung tissues 5 cm away from the lung lesions (29 cases in the lung cancer group and 32 cases in the normal group). The expression of autophagy-related proteins ATG5, LC3B, and p62 in lung tissues were measured by Western blot, and mRNA expression of ATG5 and p62 in the lung tissues were measured by real-time PCR.Results Western blot analysis showed that the expression of ATG5 and p62 in lung cancer group were significantly higher than those in normal group (P<0.05). However, the expression of LC3B in lung cancer group was significantly lower than that in normal group (P<0.05). Real-time PCR analysis found that the mRNA expression of ATG5 and p62 in lung cancer group were significantly higher than those in normal group (P<0.05). The expression of ATG5, LC3B and p62 had no relationship with gender, age, smoking history, tumor location, tumor size, clinicopathological classification, differentiation or TNM stage. The expression of ATG5 had statistical significance in lymph node metastasis (P<0.05), but there was no difference for LC3B or p62 in lymph node metastasis (P>0.05).Conclusions Autophagy plays a role in the tumorigenesis of lung cancer. If it’s possible to regulate and control autophagy-related genes and proteins effectively, it may supply new insights or targets into treatment for lung cancer patients.

Citation： SUN Yuqing, CHENG Pengpeng, YU Haiyang, WANG Mengmeng, GUAN Wenbin, HAN Fengfeng. Expression of autophagy-related proteins and genes in patients with non-small cell lung cancer. Chinese Journal of Respiratory and Critical Care Medicine, 2019, 18(5): 447-451. doi: 10.7507/1671-6205.201811038 Copy

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2.	Guo HS, Maneka C, Luc R. Atg5 disassociates the V1V0-ATPase to promote exosome production and tumor metastasis independent of canonical macroautophagy. Dev Cell, 2017, 43(6): 716-730.
3.	Parzych KR, Klionsky DJ. An overview of autophagy: morphology, mechanism, and regulation. Antioxid Redox Signal, 2014, 20(3): 460-473.
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7.	Lee JG, Shin JH, Shim HS, et al. Autophagy contributes to the chemo-resistance of non-small cell lung cancer in hypoxic conditions. Respir Res, 2015, 16: 138.
8.	Wang X, Du Z, Li L, et al. Beclin 1 and p62 expression in non-small cell lung cancer: relation with malignant behaviors and clinical outcome. Int J Clin Exp Pathol, 2015, 8(9): 10644-10652.
9.	Yan XY, Zhang Y, Zhang JJ, et al. p62/SQSTM1 as an oncotarget mediates cisplatin resistance through activating RIP1-NF-κB pathway in human ovarian cancer cells. Cancer Sci, 2018, 108(7): 1405-1413.
10.	Lam HC, Baglini CV, Lope AL, et al. p62/SQSTM1 cooperates with hyperactive mTORC1 to regulate glutathione production, maintain mitochondrial integrity, and promote tumorigenesis. Cancer Res, 2017, 77(12): 3255-3267.
11.	Jiang L, Liang X, Liu M, et al. Reduced expression of liver kinase B1 and Beclin1 is associated with the poor survival of patients with non-small cell lung cancer. Oncol Rep, 2014, 32(5): 1931-1938.
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13.	全昱冲, 张钗红. ATG5 在恶性肿瘤中的相关研究. 世界最新医学信息文摘, 2017, 17(93): 52.
14.	曾晓刚, 葛明建. ATG5 敲低后抑制人肺癌细胞 H1299 自噬并增强南蛇藤素诱导的细胞凋亡. 基础医学与临床, 2017, 37(4): 531-536.
15.	Moscat J, Diaz Meco MT. P62 at the cross-roads of autophagy, apoptosis, and cancer. Cell, 2009, 137(6): 1001-1004.
16.	Duran A, Linares JF, Galvez AS, et al. The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis. Cancer Cell, 2008, 13(4): 343-354.
17.	Seibenhener ML, Du Y, Diaz-Meco MT, et al. A role for sequestosome 1/p62 in mitochondrial dynamics, import and genome integrity. Biochim Biophys Acta, 2013, 1833(3): 452-459.
18.	Linares JF, Amanchy R, Greis K, et al. Phosphorylation of p62 by cdk1 controls the timely transit of cells through mitosis and tumor cell proliferation. Mol Cell Biol, 2011, 37(15): 105-117.
19.	吴楠, 闵鹤鸣, 屈惠莹, 等. 自噬基因 pULK、PI3KC3 在非小细胞肺癌中的表达及相关性研究. 天津医药, 2015, 43(6): 635-638.
20.	Inoue D, Suzuki T, Mitsuishi Y, et al. Accumulation of p62/SQSTM1 is associated with poor prognosis in patients with lung adenocarcinoma. Cancer Sci, 2012, 103(4): 760-766.
21.	王璁, 李永文, 李颖, 等. LC-3 和 P62 在非小细胞肺癌中的表达及其临床特征分析. 中国肺癌杂志, 2018, 21(6): 445-450.
22.	Chen N, Karantza-Wadsworth V. Role and regulation of autophagy in cancer. Biochim Biophys Acta, 2009, 1793(9): 1516-1523.
23.	White E, DiPaola RS. The double-edged sword of autophagy modulation in cancer. Clin Cancer Res, 2009, 15(17): 5308-5316.

1. Li Y, Yu HY, Wang MM, et al. Biochanin A induces S phase arrest and apoptosis in lung cancer cells. Biomed Res Int, 2018: 3545376.
2. Guo HS, Maneka C, Luc R. Atg5 disassociates the V1V0-ATPase to promote exosome production and tumor metastasis independent of canonical macroautophagy. Dev Cell, 2017, 43(6): 716-730.
3. Parzych KR, Klionsky DJ. An overview of autophagy: morphology, mechanism, and regulation. Antioxid Redox Signal, 2014, 20(3): 460-473.
4. Gianchecchi E, Delfino DV, Fierabracci A. Recent insights on the putative role of autophagy in autoimmune diseases. Autoimmun Rev, 2014, 13(3): 231-241.
5. 於海洋, 李妍, 管雯斌, 等. 慢性阻塞性肺疾病患者肺组织中自噬相关基因和蛋白的表达. 上海医学, 2017, 40(2): 94-999.
6. Ndoye A, Budina-Kolomets A, Kugel CH 3^rd, et al. ATG5 mediates a positive feedback loop between Wnt signaling and autophagy in melanoma. Cancer Res, 2017 77(21): 5873-5885.
7. Lee JG, Shin JH, Shim HS, et al. Autophagy contributes to the chemo-resistance of non-small cell lung cancer in hypoxic conditions. Respir Res, 2015, 16: 138.
8. Wang X, Du Z, Li L, et al. Beclin 1 and p62 expression in non-small cell lung cancer: relation with malignant behaviors and clinical outcome. Int J Clin Exp Pathol, 2015, 8(9): 10644-10652.
9. Yan XY, Zhang Y, Zhang JJ, et al. p62/SQSTM1 as an oncotarget mediates cisplatin resistance through activating RIP1-NF-κB pathway in human ovarian cancer cells. Cancer Sci, 2018, 108(7): 1405-1413.
10. Lam HC, Baglini CV, Lope AL, et al. p62/SQSTM1 cooperates with hyperactive mTORC1 to regulate glutathione production, maintain mitochondrial integrity, and promote tumorigenesis. Cancer Res, 2017, 77(12): 3255-3267.
11. Jiang L, Liang X, Liu M, et al. Reduced expression of liver kinase B1 and Beclin1 is associated with the poor survival of patients with non-small cell lung cancer. Oncol Rep, 2014, 32(5): 1931-1938.
12. Schläfli AM, Adams O, Galván JA1, et al. Prognostic value of the autophagy markers LC3 and p62/SQSTM1 in early-stage non-small cell lung cancer. Qncotarget, 2016, 7(26): 39544-39555.
13. 全昱冲, 张钗红. ATG5 在恶性肿瘤中的相关研究. 世界最新医学信息文摘, 2017, 17(93): 52.
14. 曾晓刚, 葛明建. ATG5 敲低后抑制人肺癌细胞 H1299 自噬并增强南蛇藤素诱导的细胞凋亡. 基础医学与临床, 2017, 37(4): 531-536.
15. Moscat J, Diaz Meco MT. P62 at the cross-roads of autophagy, apoptosis, and cancer. Cell, 2009, 137(6): 1001-1004.
16. Duran A, Linares JF, Galvez AS, et al. The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis. Cancer Cell, 2008, 13(4): 343-354.
17. Seibenhener ML, Du Y, Diaz-Meco MT, et al. A role for sequestosome 1/p62 in mitochondrial dynamics, import and genome integrity. Biochim Biophys Acta, 2013, 1833(3): 452-459.
18. Linares JF, Amanchy R, Greis K, et al. Phosphorylation of p62 by cdk1 controls the timely transit of cells through mitosis and tumor cell proliferation. Mol Cell Biol, 2011, 37(15): 105-117.
19. 吴楠, 闵鹤鸣, 屈惠莹, 等. 自噬基因 pULK、PI3KC3 在非小细胞肺癌中的表达及相关性研究. 天津医药, 2015, 43(6): 635-638.
20. Inoue D, Suzuki T, Mitsuishi Y, et al. Accumulation of p62/SQSTM1 is associated with poor prognosis in patients with lung adenocarcinoma. Cancer Sci, 2012, 103(4): 760-766.
21. 王璁, 李永文, 李颖, 等. LC-3 和 P62 在非小细胞肺癌中的表达及其临床特征分析. 中国肺癌杂志, 2018, 21(6): 445-450.
22. Chen N, Karantza-Wadsworth V. Role and regulation of autophagy in cancer. Biochim Biophys Acta, 2009, 1793(9): 1516-1523.
23. White E, DiPaola RS. The double-edged sword of autophagy modulation in cancer. Clin Cancer Res, 2009, 15(17): 5308-5316.

Chinese Journal of Respiratory and Critical Care Medicine

Expression of autophagy-related proteins and genes in patients with non-small cell lung cancer

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