LPAR5 stimulates the malignant progression of non-small-cell lung carcinoma by upregulating MLLT11

H.-P. Zhang, Q.-K. Chen, J.-F. Xu

Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. edward2020@aliyun.com

---

• Oncology

OBJECTIVE: This study aims to explore the diagnostic and prognostic values of Lysophosphatidic acid receptor 5 (LPAR5) in non-small-cell lung cancer (NSCLC) and its regulatory effects on biological functions of NSCLC cells.

PATIENTS AND METHODS: NSCLC and adjacent non-tumoral tissues were collected for analyzing differential levels of LPAR5 by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Clinical information of recruited NSCLC patients was collected for assessing the diagnostic and prognostic values of LPAR5. In vitro regulation of LPAR5 on proliferative and migratory potentials of H1299 and SPC-A1 cells was examined by Cell Counting Kit-8 (CCK-8) and transwell assay, respectively. In addition, in vivo regulation of LPAR5 on the growth rate of NSCLC in nude mice was detected by tumorigenicity assay. The interaction between LPAR5 and its downstream target MLLT11 was determined by rescue experiments.

RESULTS: LPAR5 was upregulated in NSCLC tissues than adjacent non-tumoral ones. High level of LPAR5 predicted higher rates of lymphatic metastasis and distant metastasis, as well as worse overall survival and progression-free survival in NSCLC. Knockdown of LPAR5 not only attenuated in vitro proliferative and migratory abilities in H1299 and SPC-A1 cells, but also slowed down in vivo growth of NSCLC in nude mice. MLLT11 was upregulated in NSCLC tissues, and displayed a positive correlation to LPAR5. Overexpression of MLLT11 was able to reverse the attenuated in vitro proliferative and migratory abilities, and the suppressed in vivo growth of NSCLC because of LPAR5 knockdown.

CONCLUSIONS: LPAR5 stimulates proliferative and migratory potentials in NSCLC by positively regulating MLLT11, which can be served as an effective diagnostic marker for early stage NSCLC.

Free PDF Download