Cell Death Differ: KDM4C promotes radiation resistance to lung cancer through an observational genetic modification

Cancer is both a genetic and an opogenetic disease, and previous studies have shown that metagenetic changes, including histogeneic modification and DNA methylation, are closely related to the development of tumors.
KDM4C (histoprotein lysine demethylase 4C, also known as JMJD2C/GASC1) is a member of the JmjC protein family, whose coding is associated with H3K9me3/2 and H3K36me3/2, and has been shown to be associated with malignant transformation of tumors.
growing evidence that KDM4C, as a candidate cancer protein, can be amplified or over-expressed in multiple cancer types.
, however, it is not clear how KDM4C regulates and functions in cancer radiotherapy resistance.
increased expression of KDM4C in lung cancer and radiation resistance associated with poor prognostication in patients is considered a major obstacle to effective radiotherapy in lung cancer.
the study, the researchers found that KDM??? Overex expression of 4C is associated with poor prognostication in lung cancer patients.
or pharmacological inhibition of the expression of KDM4C can weaken tumor occurrence and the production of radiotherapy resistance.
Addition, the researchers found that KDM4C was able to increase the expression of TGF-beta2 by directly reducing H3K9me3 levels in the TGF-beta-2 promoter region, activating the Smamad/ATM/Chk2 signal transduct path and ultimately giving lung cancer cells radiation resistance.
study schematic affinity and purification experiments further identified the de-ubiganase USP9X as a key binding partner for de-ubixinization and maintenance of stability of KDM4C.
more importantly, knocking out USP9X disrupts the stability of KDM4C in lung cancer cells, thereby impairing the TGF-beta 2/Smad signal transducting path and the production of radiotherapy resistance.
in summary, the results show that USP9X-mediated KDM4C de-ubixination activates the TGF-beta 2/Smad signal transduct path and promotes radiotherapy resistance.
, targeting KDM4C may be a potential radiosensitive strategy during the treatment of lung cancer.