AIM2 promotes non‐small‐cell lung cancer cell growth through inflammasome‐dependent pathway

Abstract

The human absent in melanoma 2 (AIM2) is considered as a DNA recognizer. AIM2 has been described as a tumor suppressor gene in the early years. But recent studies suggested that it functions as an oncogene in several cancers. However, its roles in non-small-cell lung cancer (NSCLC) remain unclear. Here we reported that AIM2 highly expressed in NSCLC cells and exhibited a tumor-promoting property both in vitro and in vivo. Besides, AIM2 short hairpin RNA (shRNA)-mediated suppression of cell proliferation was triggered by the accumulation of cells at the G2/M phase.Knockdown of AIM2 reduced the inflammasome formation, while overexpression of AIM2 or stimulation by poly(dA:dT) induced the inflammasome formation. Interestingly, blockade of the inflammasome by caspase-1 inhibitor VX-765 or ASC small interfering RNA (siRNA) abolished the effects brought by AIM2 shRNA and AIM2 plasmid. In summary, our results revealed that AIM2 functioned as an oncogene in NSCLC in an inflammasome-dependent way.

AIM2 in health and disease: Inflammasome and beyond

“…147 Unlike in colorectal cancers, AIM2 has been found to function as an oncogene that promotes growth and proliferation in an inflammasome-dependent manner in lung carcinoma cell lines such as A549 and H460. 90 In line with this, high expression of AIM2 has been observed in NSCLC tissue and cell lines. 148 Furthermore, it has been recently reported that AIM2 expression positively correlates with the growth and proliferation of NSCLC cells in vitro and in vivo and that AIM2 expression in NSCLC tumors is associated with poor prognosis in patient.…”

“…High expression of AIM2 is observed in non-small cell lung cancer (NSCLC), and AIM2 plays both inflammasome-dependent and inflammasome-independent roles in NSCLC. [90][91][92] In an in vitro study with lung cancer epithelial cell lines A549 and H460, the depletion of AIM2 and ASC with shRNA and siRNA, respectively, as well as inhibition of caspase-1 with VX765, inhibited cell growth and metastasis. Furthermore, the depletion of AIM2 and ASC and the inhibition of caspase-1 promoted cell-cycle arrest at G2/M phase, which paralleled with cyclin B1 reduction in these cell lines.…”

“…Furthermore, the depletion of AIM2 and ASC and the inhibition of caspase-1 promoted cell-cycle arrest at G2/M phase, which paralleled with cyclin B1 reduction in these cell lines. 90 Similarly, luteolin (a natural flavonoid) treatment reduced the expression of AIM2, and the activation of caspase-1 and IL-1β in A549 and H460 cell lines as well as in their xenografts in mice. Furthermore, luteolin depleted cyclin B1 and promoted growth arrest at the G2/M phase in these cell lines.…”

Prognostic Inflammasome-Related Signature Construction in Kidney Renal Clear Cell Carcinoma Based on a Pan-Cancer Landscape

“…However, increasing studies have also suggested their tumor-promoting property, corresponding to our findings. For instance, AIM2 improved proliferation of non-small-cell lung cancer (NSCLC) cells via inflammasome-dependent pathway [41]. Knockdown of either AIM2 or IFI16 in oral squamous cell carcinoma cells reduced cell growth [42].…”

Expression of AIM2 in rheumatoid arthritis and its role on fibroblast-like synoviocyte

“…AIM2 pathway plays a putative role in tumorigenic reversion and may control cell proliferation 15 . AIM2 expression suppressed the proliferation and tumorigenicity of human breast cancer cells, and that AIM2 gene therapy inhibited mammary tumor growth in an orthotopic tumor model.…”