Circular RNA (circRNA) is a type of noncoding RNA that can interact with miRNAs to regulate gene expression. However, little is known concerning circRNA, which is crucial in the pathogenesis of lung cancer. To date, limited studies have explored the role of circ_0044516 in lung cancer progression. Recently, we observed that circ_0044516 expression levels were obviously elevated in lung cancer tissues and cells. A549 and SPCA1 cells were transfected with circ_0044516 siRNA. We observed that knockdown of circ_0044516 dramatically repressed cell proliferation, increased cell apoptosis, and repressed the cell cycle. Moreover, A549 and SPCA1 cell migration and invasion abilities were greatly repressed by circ_0044516 siRNA. Due to accumulating evidence demonstrating the vital role of cancer stem cells, their mechanism of involvement has drawn increasing attention in tumor progression and metastasis research. We also found that cancer stem cell properties were restrained by silencing circ_0044516 in A549 and SPC-A1 cells. Moreover, in vivo xenograft experiments showed that circ_0044516 downregulation reduced tumor growth. Mechanistically, in lung cancer and using bioinformatics, we demonstrated that circ_0044516 sponges miR-136 targeting MAT2A. Furthermore, rescue assays were carried out to identify that circ_0044516 modulates cell proliferation, invasion, and stemness by regulating miR-136 and MAT2A in lung cancer. In summary, our study revealed that the circ_0044516/miR-136/MAT2A axis is involved in lung cancer progression. Our findings may provide novel targets for diagnosis and therapeutic intervention in lung cancer patients.

Background: Lung cancer is a common malignant neoplasm worldwide. Phosphoinositide-3-kinase, regulatory subunit 1 (PIK3R1) plays as a therapeutic target in many cancers. The role PIK3R1 plays in lung cancer still remains unclear. Our study aims to explore the role of PIK3R1 in lung cancer.Methods: We used quantitative real-time PCR (qPCR) to detect the PIK3R1 mRNA expression level in our 20 paired lung cancer patients. We then used A549sh-PIK3R1, H1299sh-PIK3R1, H1650LV-PIK3R1, H292LV-PIK3R1, A549sh-PIK3R1+LV-PIK3R1 and H1299sh-PIK3R1+LV-PIK3R1 cells for in vitro analysis. Cell viability assay was used to detect the ability of PIK3R1 in regulating proliferation of lung cancer. Western blot analysis was used to detect the PIK3R1 protein expression level and proteins in PI3K/AKT/mTOR signaling pathway.Results: PIK3R1 mRNA expression level was higher in tumour tissues than the corresponding adjacent noncancerous among the 20 lung cancer patients. Increased PIK3R1 promoted lung cancer proliferation and downregulated PIK3R1 inhibited lung cancer proliferation. Furthermore, PIK3R1 downregulation suppressed p-PI3K, p-Akt, and p-mTOR in A549sh-PIK3R1 and H1299sh-PIK3R1 cells. Overexpressed of PIK3R1 upregulated p-PI3K, p-Akt, and p-mTOR in H1650LV-PIK3R1 and H292LV-PIK3R1 cells. Cell viability was increased in both A549 and H1299 cells following sh-PIK3R1+LV-PIK3R1 co-transfection, thus reversed the effect of sh-PIK3R1 on cell proliferation.Conclusions: We identified that overexpressed of PIK3R1 could promote lung cancer proliferation via PI3K/AKT/mTOR signaling pathway, thus may provide PIK3R1 as a therapeutic target for effective strategy in lung cancer.

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