The role of circular RNA in cancer is emerging. A newly reported circular RNA HIPK3 (circHIPK3) is critical in cell proliferation of various cancer types, although its role in non-small cell lung cancer (NSCLC), has yet to be elucidated. Our results provided evidence that silencing of circHIPK3 significantly impaired cell proliferation, migration, invasion and induced macroautophagy/autophagy. Mechanistically, we uncovered that autophagy was induced upon loss of circHIPK3 via the MIR124-3p-STAT3-PRKAA/AMPKa axis in STK11 mutant lung cancer cell lines (A549 and H838). STAT3 abrogation as well as transfection with a MIR124-3p mimic, recapitulated the induction of autophagy. We also demonstrated antagonistic regulation on autophagy between circHIPK3 and linear HIPK3 (linHIPK3). We therefore propose that the ratio between circHIPK3 and linHIPK3 (C:L ratio) may reflect autophagy levels in cancer cells. We observed that a high C:L ratio (>0.49) was an indicator of poor survival, especially in advanced-stage NSCLC patients. These results support that circHIPK3 is a key autophagy regulator in a subset of lung cancer and has potential clinical use as a prognostic factor. The circular RNA HIPK3 (circHIPK3) functions as an oncogene and autophagy regulator may potential use as a prognostic marker and therapeutic target in lung cancer.

中文翻译：

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在STK11突变型肺癌中，环状RNA circHIPK3通过MIR124-3p-STAT3-PRKAA /AMPKα信号传导调节自噬。

环状RNA在癌症中的作用正在兴起。尽管尚未阐明其在非小细胞肺癌（NSCLC）中的作用，但新报道的环状RNA HIPK3（circHIPK3）在各种癌症类型的细胞增殖中均至关重要。我们的结果提供了证据，证明circHIPK3沉默显着损害细胞增殖，迁移，侵袭并诱导巨自噬/自噬。从机理上讲，我们发现在STK11突变型肺癌细胞系（A549和H838）中，通过MIR124-3p -STAT3-PRKAA / AMPKa轴缺失circHIPK3后会诱导自噬。STAT3废除以及MIR124-3p的转染模仿，概括了自噬的诱导。我们还证明了在circHIPK3和线性HIPK3（linHIPK3）之间自噬的拮抗作用。因此，我们建议circHIPK3和linHIPK3之间的比率（C：L比率）可能反映癌细胞中的自噬水平。我们观察到高的C：L比（> 0.49）是不良生存的指标，尤其是在晚期NSCLC患者中。这些结果支持circHIPK3是肺癌子集中的关键自噬调节剂，并具有潜在的临床应用作为预后因素。环状RNA HIPK3（circHIPK3） 作为癌基因的功能和自噬调节剂可能潜在地用作肺癌的预后标志物和治疗靶标。