Fig 2: miR-183-5p enriched M2-TAM-Exo heightened the proliferation and metastasis of CC cells in vivo. The xenograft model was constructed to observe the effect of miR-183-5p in vivo. (A) The figure of xenograft tumor. (B, C) Tumor volume and weight. (D) H&E staining. (E) The miR-183-5p profile in the xenograft tumor was determined verified by qRT-PCR. (F, G) The levels of Ki67 and THEM4 were compared by IHC. (H) The relative expression of THEM4, AKT and p-NF-κB in tumor tissues of each group was tested by WB. *P <0.05, **P < 0.01, ***P <0.001 (vs. M2-TAM group). N=3.

Fig 3: Overexpressing THEM4 abated the M2-TAMmiR-183-5p exosomes induced malignant progression of CC cells. The THEM4 overexpression model was constructed in SW480 cells, which were then deal with exosomes from M2-TAMmiR-NC or M2-TAMmiR-183-5p. (A, B) The miR-183-5p and THEM mRNA profiles in SW480 cells were monitored by qRT-PCR. (C)The THEM4, AKT, NF-κB levels in SW480 cells were detected by WB. (D) CCK-8 assay was employed to examine CC cell proliferation. (E) Colony formation assay was applied to detect the ability of cells to form colonies. (F) Wound healing test determined cell migration. (G) Cell invasion was monitored by Transwell assay. (H) Apoptosis was determined by FCM. **P < 0.01, ***P < 0.001 (vs. The M2-TAM miR-NC group), ns, P > 0.05, ^P < 0.05, ^^P < 0.01, ^^^P < 0.001 (vs. The M2-TAM miR-183-5p+Vector group). N=3.

Fig 4: Overexpressing THEM4 dampened the malignant phenotypes of CC. THEM4 overexpression model was established on SW480 cells. (A) The THEM4 expression was detected by WB. (B) CCK-8 assay was employed to examine CC cell proliferation. (C) Colony formation assay was applied to detect the ability of cells to form colonies. (D) Wound healing test determined cell migration. (E) Cell invasion was monitored by Transwell assay. (F) Apoptosis was determined by FCM. (G) Akt and NF-κB levels were compared by WB. *P < 0.05, **P < 0.01, ***P < 0.001 (vs. The M2-TAM miR-NC group). N=3.

Fig 5: Reduction of CTMP expression in cells with overexpression of Zic2. (A) representative images of Western blot analysis of various groups. B: quantitative data of Zic2 abundance. Results are median with 95% CI with the presence of values of individual sample (n = 9–10). (C) quantitative data of CTMP abundance. Results are mean ± SD (n = 7–9) with the presence of values of individual samples. Experiments were conducted three times independently with two to three sets of samples each time. Normality was tested by the Shapiro–Wilk test. Statistical analysis was done by one‐way ANOVA.