In the early, online edition of the Proceedings of the National Academy of Sciences, researchers from Italy, the US, and Switzerland describe a microRNA contributing to progression and treatment response in forms of melanoma marked by activating BRAF mutations. Using available data, the team attempted to find miRNAs related to progression in these melanomas. Of four candidate miRNAs found in the analysis, one — miR-579-3p — showed dwindling expression during progression and in patients with poor survival. The investigators' follow-up analyses suggest miR-579-3p regulates BRAF and another oncoprotein, MDM2. While its typical expression seems to suppress BRAF and MEK inhibitor resistance, they note, expression of the miRNA is dialed down in tumors that no longer respond to targeted therapy.
A team from the US and France focus on a process called oncogene-induced senescence, which stops normal, pre-malignant cells from dividing unchecked in response to oncogenic signals such as activated HRAS or BRAF. With the help of cancer cell lines expressing activated HRAS or BRAF, the researchers saw signs that cells that previously responded to oncogene-induced senescence can escape this growth arrest — a process marked by enhanced oncogene expression and chromatin shifts that unleash expression of the telomere- and cancer-related the enzyme-coding gene hTERT. "[O]ur data demonstrate that cells arrested in [oncogene-induced senescence] retain the potential to escape senescence by mechanisms that involve derepression of hTERT expression," they write.
Finally, UK researchers report on a role for the DNA damage checkpoint gene ATM in plant seed germination and genome stability. In its effort to begin untangling the role of double-strand break repair and germination progression in aging Arabidopsis plants, the team did a series of experiments starting with transgenic Arabidopsis lines prone to double-strand DNA breaks. The results suggest that sensor kinase enzymes that mediate DNA damage checkpoint activity also help to strike a balance between aging, germination progress, and genome stability. In mutants missing ATM, for example, the investigators identified faster germination with chromosomal abnormalities in older plants, while the presence of ATM slowed germination and maintained genome integrity.