RNase L is an essential component in
interferon (IFN)-mediated
antiviral signaling that showed antitumor effects in
cancer.
Cancer immunotherapy based on
interferon has achieved encouraging results that indicate an applicable potential for
cancer therapy. Here we showed that function of
RNase L, though highly upregulated, was functionally impaired both in nuclear and cytoplasm in
lung cancer cells. In normal lung epithelial cells,
RNase L activation induced by 2-5A promoted nuclear condensation, DNA cleavage, and cell apoptosis, while in
lung cancer cells, these processes were inhibited and
RNase L-mediated downregulation of
fibrillarin,
Topo I and
hnRNP A1 was also impaired in
lung cancer cells. Moreover, the impairment of
RNase L in
lung cancer cells was due to the elevated expression of RLI. Application of IFN-γ to
lung cancer cells led to enhanced expression of
RNase L that compensated the RLI inhibition and restored the cytoplasmic and nuclear function of
RNase L, leading to apoptosis of
lung cancer cells. Thus, the present study discovered the impaired function and mechanism of
RNase L in
lung cancer cells and proved the efficacy of IFN-γ in restoring
RNase L function and inducing apoptosis in the
lung cancer cell. These results indicated the
RNase L as a therapeutic target in
lung cancer cells and
immunotherapy of IFN-γ may serve as an adjuvant to enhance the efficacy.