CD73/NT5E is a target of miR-30a-5p and plays an important role in the pathogenesis of non-small cell lung cancer.
CD73 (ecto-5'-nucleotidase) is implicated in the development of many types of cancer. CD73 inhibitors are currently being tested in clinical trials for the treatment of cancer. Understanding the molecular and cellular actions of CD73 inhibitors is the key to improving this line of therapy.



Quantitative real-time PCR (qRT-PCR) was used to detect the expression of CD73 and miR-30a-5p; Western blot and immunohistochemical assays were used to investigate the levels of CD73 and other proteins. Flow cytometry was used to determine cell cycle stage and apoptosis. CCK-8 and clonogenic assays were used to investigate cell proliferation. Wound healing, migration and invasion assays were used to investigate the motility of cells. A lung carcinoma xenograft mouse model was used to investigate the in vivo effects of CD73 and miR-30a-5p.



In the present study, we found that CD73 is overexpressed and miR-30a-5p is underexpressed in non-small cell lung cancer tissues compared with adjacent noncancerous. Further, we showed that CD73 is a direct target of miR-30a-5p by luciferase reporter assays, qRT-PCR and western blot analysis. We also found that overexpression of miR-30a-5p in these non-small cell lung cancer cell lines inhibited cell proliferation in vitro and in vivo. Moreover, the epithelial-to-mesenchymal phenotype was suppressed and cell migration and invasion were inhibited; these effects were brought about via the EGF signaling pathway.



Our findings reveal a new post-transcriptional mechanism of CD73 regulation via miR-30a-5p and EGFR-related drug resistance in non-small cell lung cancer.
Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou, 215006, People's Republic of China.|Institute of Respiratory Diseases, Soochow University, Suzhou, 215006, China.
Jianjie
J
Zhu
Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou, 215006, People's Republic of China.|Institute of Respiratory Diseases, Soochow University, Suzhou, 215006, China.
Yuanyuan
Y
Zeng
Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Wei
W
Li
Department of Cardiothoracic Surgery, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Hualong
H
Qin
Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou, 215123, China.
Zhe
Z
Lei
Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou, 215006, People's Republic of China.
Dan
D
Shen
Department of Pathology, the First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Dongmei
D
Gu
Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou, 215006, People's Republic of China. huang_jian_an@yeah.net.|Institute of Respiratory Diseases, Soochow University, Suzhou, 215006, China. huang_jian_an@yeah.net.
Jian-An
JA
Huang
Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou, 215006, People's Republic of China. liuzeyisuda@163.com.|Institute of Respiratory Diseases, Soochow University, Suzhou, 215006, China. liuzeyisuda@163.com.
Zeyi
Z
Liu
D020413:3' Untranslated Regions; D015720:5'-Nucleotidase / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects
D020413:3' Untranslated Regions; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D015720:5'-Nucleotidase
CD73; EGFR; Non-small cell lung cancer; miR-30a-5p; miRNA