Circular RNA circ-PTEN elevates PTEN inhibiting the proliferation of non-small cell lung cancer cells

Abstract

Phosphatase and tensin homolog (PTEN) is a well-known tumor suppressor in various cancer types, including non-small cell lung cancer (NSCLC). Circular RNA (circRNA) has recently been proven to be strongly linked with cancer progression. Here, we aimed to investigate the biological relevance and clinical significance of circRNA derived from PTEN in NSCLC. We found that circ-PTEN (hsa_circ_0094342) was significantly decreased in NSCLC tissues and serum, which was attributed to the upregulation of RNA-binding protein DHX9. Low circ-PTEN was linked with malignant clinical features and poor outcome. Exogenous expression of circ-PTEN markedly inhibited NSCLC cell proliferation in vitro as well as retarded tumor growth in vivo. Circ-PTEN increased the expression of its host gene PTEN via acting as a sponge for miR-155 and miR-330-3p, leading to the inactivation of the carcinogenic PI3K/AKT signaling pathway. The xenograft tumor model also indicated the existence of circ-PTEN/miR-155/miR-330-3p/PTEN regulatory axis in vivo. Our data for the first time demonstrate that circ-PTEN functions as a tumor-inhibiting circRNA in NSCLC through post-transcriptionally regulating PTEN, hinting a promising diagnostic/prognostic biomarker as well as therapeutic target for NSCLC patients.

Knockdown of hsa_circ_0000729 Inhibits the Tumorigenesis of Non-Small Cell Lung Cancer Through Mediation of miR-1281/FOXO3 Axis

“…For instance, Yi et al found that hsa_circ_0001806 overexpression could increase the growth, migration and invasion of NSCLC cells via mediation of miR-1182/NOVA2 axis; 6 Wang et al indicated that circ-PTEN upregulation could suppress the proliferation of NSCLC cells through activation of PTEN. 7 Meanwhile, it has been revealed that hsa_circ_0000729 was significantly upregulated in lung adenocarcinoma (LUAD). 8 LUAD is the main subtype of NSCLC.…”

Circular RNA circβ‐catenin aggravates the malignant phenotype of non‐small‐cell lung cancer via encoding a peptide

“…To further confirm the functions of circβ‐catenin in NSCLC cells, Lv‐circβ‐catenin and Lv‐NC were designed and synthesized. Upregulation of circRNAs can change the characteristics of tumor 31‐34 . The characteristics of tumor include many aspects, such as proliferation, migration, invasion, and drug resistance 28,29,35,36 .…”

“…CircRNAs have received widespread attention in recent years 46,47 . The extensive expression patterns of circRNAs strongly illuminate their role in oncogenic regulation 33,35,46 . CircRNAs are ubiquitous in the occurrence and development of NSCLC.…”

“…46,47 The extensive expression patterns of cir-cRNAs strongly illuminate their role in oncogenic regulation. 33,35,46 CircRNAs are ubiquitous in the occurrence and development of NSCLC. For example, the expression of circSMARCA5 is negatively correlated with the tumor size of NSCLC, lymph node metastasis and TNM staging.…”

“…Upregulation of circRNAs can change the characteristics of tumor. [31][32][33][34] The characteristics of tumor include many aspects, such as proliferation, migration, invasion, and drug resistance. 28,29,35,36 Therefore, we aimed to explore whether circβ-catenin upregulation could change the characteristics of NSCLC cells.…”