CircRNA circ_POLA2 promotes lung cancer cell stemness via regulating the miR‐326/GNB1 axis

Abstract

Circular RNAs (CircRNAs) are a group of noncoding RNAs that have essential function in the development and progression of various cancers. The expression pattern and function of circRNA in lung cancer is not fully understood. In the present study, we aimed to investigate the expression profiles and underlying mechanism of circRNA circ_POLA2 in lung cancer cell stemness. Circ_POLA2 was highly expressed in lung cancer tissues and predicted a poor prognosis in lung cancer patients. Knockdown of circ_POLA2 inhibited the stemness of lung cancer cells, which is evident by the decreased sphere‐formation ability, ALDH1 activity, and stemness marker expression, but had no effects on cell viability. Mechanistically, circ_POLA2 functioned as a ceRNA by sponging miR‐326. Furthermore, miR‐326 negatively regulated G protein subunit beta 1 (GNB1) expression by targeting its 3′‐UTR (untranslated region). Intriguingly, we found that GNB1 was overexpressed and associated with poor prognosis in lung cancer patients. Overexpression of GNB1 could antagonize the inhibitory effect of circ_POLA2 knockdown on lung cancer cell stemness. In conclusion, circ_POLA2 promotes lung cancer cell stemness and progression via regulating the miR‐326/GNB1 axis, which might serve as a novel therapeutic target for lung cancer patients.

CircRNA circ_POLA2 is Upregulated in Acute Myeloid Leukemia (AML) and Promotes Cell Proliferation by Suppressing the Production of Mature miR-34a

“…In a recent study, circ_POLA2 was reported to be significantly upregulated in lung cancer and positively regulated the stemness of lung cancer cells. 14 Moreover, mechanism studies showed that circ_POLA2 may upregulate G protein subunit beta 1 by serving as an endogenous competing RNA for miR-326. 14 This study is the first to explore the involvement of circ_POLA2 in AML.…”

“… 14 Moreover, mechanism studies showed that circ_POLA2 may upregulate G protein subunit beta 1 by serving as an endogenous competing RNA for miR-326. 14 This study is the first to explore the involvement of circ_POLA2 in AML. We found that circ_POLA2 was upregulated in AML.…”

“… 13 Unfortunately, the functions of most circRNAs in cancer biology are unknown. CircRNA circ_POLA2 has been identified as an oncogene in lung cancer, 14 while its role in other malignancies is unknown. Our preliminary microarray analysis observed an altered expression of circ_POLA2 and its close correlation with miR-34a, which plays a tumor suppressive role in AML.…”

circRNA circ_POLA2 increases microRNA‑31 methylation to promote endometrial cancer cell proliferation

“…Therefore, circRNAs may serve as potential targets for EC treatment. A previous study described a novel circRNA, circ_POLA2, with congenic functions in lung and cervical cancers (13,14). Our previous study, using deep sequencing analysis revealed altered circ_POLA2 expression level in EC, with an inverse correlation with microRNA (miR)-31, which has also been associated with cancer biology (15).…”

Biogenesis, Functions, and Role of CircRNAs in Lung Cancer

“…Circ_POLA2 is significantly upregulated in lung cancer cells and tissues, and promotes lung cancer progression via miR-326/GNB1 axis. 48 GNB1 is a direct target of miR-326 and necessary for the miR-326-mediated suppression on the stemness of lung cancer cells. In conclusion, circ_POLA2 plays a potential regulatory role via regulating the miR-326/GNB1 axis in lung cancer cell stemness.…”