Taken together, our results provide the first evidence that high expression of ARNT2 inhibited proliferation of GC cells and affected tumor aggressiveness in GC patients.
Moreover, PM<sub>2.5</sub> increased the production of ARNT2 and the inactivation of the tumor suppressor B56<i>γ</i>-PP2A, which was followed by the activation of <sup>ps727</sup>STAT3 and the enhancement of invasive ability by MMP-2.
Moreover, ARNT2 expression correlated with a tumorigenic molecular signature at both the tissue level within the tumor core and at the single cell level in the patients' tumors.
High intratumoral of ARNT2 level was well correlated with longer overall survival (OS) and lower tumor to recurrence (TTR) of HCC patients after resection.
Moreover, in vivo study showed that attenuated ARNT2 expression in HCC827 cells greatly promoted tumor growth, while overexpressed ARNT2 remarkably inhibited tumor growth in a HCC827 xenograft model.
Similar to human AIP-deficient pituitary adenomas, immunohistochemical studies showed that expression of aryl hydrocarbon receptor nuclear translocator 1 or 2 (ARNT or ARNT2) protein was lost in the mouse tumors, suggesting that mechanisms of AIP-related tumorigenesis involve aberrant ARNT function.