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Joyce F. Liu, MD, MPH
Joyce F. Liu, MD, MPH
Posted: Monday, March 3, 2025
Resistance to chemotherapy remains a persistent challenge in the treatment of ovarian cancer, but a recent study identified long noncoding RNA LOC730101 as a potential marker to help overcome chemoresistance.
In the study, published in Cell Death and Disease, Yancheng Zhong, PhD, of the Hunan University of Chinese Medicine, Changsha, and colleagues found that this RNA transcript may play a significant role of in modulating drug sensitivity in ovarian cancer cells. LOC730101 is downregulated in platinum-resistant ovarian cancer tissues. According to the study authors, when overexpressed, this RNA transcript substantially enhances chemotherapy-induced apoptosis, potentially improving the effectiveness of platinum compounds and PARP inhibitors.
Mechanistically, LOC730101 exerts its function through interactions with key proteins involved in autophagy and DNA damage repair. Specifically, the study demonstrated that LOC730101 binds to Beclin-1 (BECN1), a crucial regulator of autophagy. By inhibiting BECN1 phosphorylation and autophagosomal complex formation, LOC730101 reduces the cancer cells’ ability to repair DNA damage, thereby sensitizing them to chemotherapy.
Further analysis revealed that LOC730101 inhibits the expression of RNF168, a ubiquitin ligase involved in histone H2A ubiquitination and DNA damage repair. Through this mechanism, LOC730101 impairs the recruitment of crucial DNA repair factors, including BRCA1 and RAD51, further compromising the cancer cells’ ability to recover from chemotherapeutic damage.
The researchers validated their findings through in vivo experiments using xenograft models. Mice with LOC730101-overexpressing tumors exhibited greater sensitivity to both cisplatin and the PARP inhibitor niraparib compared with control groups. These findings suggest that increasing LOC730101 expression or mimicking its effects pharmacologically may enhance the efficacy of existing ovarian cancer treatments.
Disclosure: For full disclosures of the study authors, visit nature.com.
