Fig 2: NRG1 promotes cell viability and proliferation. (A) Knockdown efficiency of NRG1, proved by quantitative real-time PCR and western blot analysis. (B) Cell viability was measured in thyroid cancer cells with depleted NRG1 expression (n=6). (C) Plate clone formation assay when NRG1 was knocked down. ***P<0.001. All experiments were repeated twice. NRG1, neuregulin 1.

Fig 3: NRG1 maintains the intracellular redox status. (A and B) Intracellular GSH and GSSG levels were determined. NRG1 elevated the GSH/GSSG ratio in thyroid cancer cells (n=3). (C and D) Decreased NRG1 expression increased intracellular ROS levels (n=3). All P<0.01. All experiments were repeated twice. **P<0.01; ***P<0.001. NRG1, neuregulin 1; GSH, glutathione; GSSG, glutathione disulfide; ROS, reactive oxygen species.

Fig 4: Schematic illustration of the mechanisms through which NRG1 regulates redox homeostasis in papillary thyroid cancer cells. NRG1 positively regulates NRF2, which upregulates ARE-related antioxidant genes (GCLC, GCLM, HMOX1, NQO1, ME1 and TXNRD). Through these mechanisms, NRG1 reduces ROS-induced oxidative stress and maintains the moderate redox homeostasis that is essential for the proliferation of papillary thyroid cancer cells. NRG1, neuregulin 1; NRF2, nuclear factor E2-related factor 2; ROS, reactive oxygen species.

Fig 5: The expression of NRF2 positively correlates with that of NRG1; data were obtained from 490 patients with thyroid cancer from the The Cancer Genome Atlas database to detect the correlation between the expression of NRG1 and NRF2. Linear regression analysis of the expression data revealed a significant positive correlation between the expression of NRF2 and NRG1 (R2=0.1001, P<0.0001). NRG1, neuregulin 1; NRF2, nuclear factor E2-related factor 2.