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Original Articles

OSR1 suppresses acute myeloid leukaemia cell proliferation by inhibiting LGR5-mediated JNK signalling

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Pages 561-568 | Received 01 Jun 2021, Accepted 29 Aug 2021, Published online: 14 Sep 2021

Figures & data

Figure 1. Reduced OSR1 in acute myeloid leukaemia. (A) mRNA expression of OSR1 was reduced in the blasts isolated from the patients and acute myeloid leukaemia cells (Kasumi-1, THP-1 and AML-193) compared to the healthy volunteers. (B) Protein expression of OSR1 was reduced in the blasts isolated from the patients and acute myeloid leukaemia cells (Kasumi-1, THP-1 and AML-193) compared to the healthy volunteers. ** vs. normal blasts, p < .01.

Figure 1. Reduced OSR1 in acute myeloid leukaemia. (A) mRNA expression of OSR1 was reduced in the blasts isolated from the patients and acute myeloid leukaemia cells (Kasumi-1, THP-1 and AML-193) compared to the healthy volunteers. (B) Protein expression of OSR1 was reduced in the blasts isolated from the patients and acute myeloid leukaemia cells (Kasumi-1, THP-1 and AML-193) compared to the healthy volunteers. ** vs. normal blasts, p < .01.

Figure 2. Silence of OSR1 contributed to acute myeloid leukaemia cell proliferation. (A) Protein expression of OSR1 was increased in Kasumi-1 and THP-1 transfected with pcDNA-OSR1 and decreased by shRNA-OSR1. (B) Over-expression of OSR1 reduced the cell viability of Kasumi-1 and THP-1, shRNA-mediated silence of OSR1 enhanced the cell viability. (C) Over-expression of OSR1 reduced the cell proliferation of Kasumi-1 and THP-1, shRNA-mediated silence of OSR1 enhanced the cell proliferation. ** vs. control, p < .01. ## vs. shNC, p < .01.

Figure 2. Silence of OSR1 contributed to acute myeloid leukaemia cell proliferation. (A) Protein expression of OSR1 was increased in Kasumi-1 and THP-1 transfected with pcDNA-OSR1 and decreased by shRNA-OSR1. (B) Over-expression of OSR1 reduced the cell viability of Kasumi-1 and THP-1, shRNA-mediated silence of OSR1 enhanced the cell viability. (C) Over-expression of OSR1 reduced the cell proliferation of Kasumi-1 and THP-1, shRNA-mediated silence of OSR1 enhanced the cell proliferation. ** vs. control, p < .01. ## vs. shNC, p < .01.

Figure 3. Silence of OSR1 suppressed acute myeloid leukaemia cell apoptosis. (A) Over-expression of OSR1 promoted the cell apoptosis of Kasumi-1 and THP-1, shRNA-mediated silence of OSR1 suppressed the cell apoptosis. (B) Over-expression of OSR1 promoted the caspase-3 activity of Kasumi-1 and THP-1, shRNA-mediated silence of OSR1 suppressed the caspase-3 activity. (C) Over-expression of OSR1 reduced protein expression of Bcl-2, while enhanced Bax and cleaved PARP, in Kasumi-1 and THP-1, shRNA-mediated silence of OSR1 enhanced Bcl-2, while reduced Bax and cleaved PARP. ** vs. control, p < .01. ## vs. shNC, p < .01.

Figure 3. Silence of OSR1 suppressed acute myeloid leukaemia cell apoptosis. (A) Over-expression of OSR1 promoted the cell apoptosis of Kasumi-1 and THP-1, shRNA-mediated silence of OSR1 suppressed the cell apoptosis. (B) Over-expression of OSR1 promoted the caspase-3 activity of Kasumi-1 and THP-1, shRNA-mediated silence of OSR1 suppressed the caspase-3 activity. (C) Over-expression of OSR1 reduced protein expression of Bcl-2, while enhanced Bax and cleaved PARP, in Kasumi-1 and THP-1, shRNA-mediated silence of OSR1 enhanced Bcl-2, while reduced Bax and cleaved PARP. ** vs. control, p < .01. ## vs. shNC, p < .01.

Figure 4. OSR1 suppressed LGR5-mediated activation of JNK pathway. (A) Over-expression of OSR1 reduced protein expression of LGR5 in Kasumi-1 and THP-1, shRNA-mediated silence of OSR1 enhanced LGR5 expression. (B) Over-expression of LGR5 attenuated OSR1 over-expression-induced decease of LGR5, JNK phosphorylation and c-myc, while aggravated OSR1 silence-induced increase of LGR5, JNK phosphorylation and c-myc. ** vs. control + NC, p < .01. ## vs. shNC or OSR1 + NC, p < .01. && vs. shNC + NC, p < .01. $$ vs. shOSR1 + NC, p < .01.

Figure 4. OSR1 suppressed LGR5-mediated activation of JNK pathway. (A) Over-expression of OSR1 reduced protein expression of LGR5 in Kasumi-1 and THP-1, shRNA-mediated silence of OSR1 enhanced LGR5 expression. (B) Over-expression of LGR5 attenuated OSR1 over-expression-induced decease of LGR5, JNK phosphorylation and c-myc, while aggravated OSR1 silence-induced increase of LGR5, JNK phosphorylation and c-myc. ** vs. control + NC, p < .01. ## vs. shNC or OSR1 + NC, p < .01. && vs. shNC + NC, p < .01. $$ vs. shOSR1 + NC, p < .01.

Figure 5. OSR1 contributed to suppression of acute myeloid leukaemia cell proliferation by inhibiting LGR5. (A) Over-expression of OSR1-induced decrease of cell viability in Kasumi-1 and THP-1 was reversed by over-expression of LGR5. (B) LGR5 over-expression weakened over-expression of OSR1-induced increase of caspase-3 activity in Kasumi-1 and THP-1. (C) LGR5 over-expression counteracted the suppressive effect of OSR1 over-expression on cell proliferation of Kasumi-1 and THP-1. ** vs. control + NC, p < .01. ## vs. OSR1 + NC, p < .01.

Figure 5. OSR1 contributed to suppression of acute myeloid leukaemia cell proliferation by inhibiting LGR5. (A) Over-expression of OSR1-induced decrease of cell viability in Kasumi-1 and THP-1 was reversed by over-expression of LGR5. (B) LGR5 over-expression weakened over-expression of OSR1-induced increase of caspase-3 activity in Kasumi-1 and THP-1. (C) LGR5 over-expression counteracted the suppressive effect of OSR1 over-expression on cell proliferation of Kasumi-1 and THP-1. ** vs. control + NC, p < .01. ## vs. OSR1 + NC, p < .01.