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Radiotherapy, as an important primary treatment, has effectively improved the survival of patients with cervical cancer (CC). Some patients, however, do not benefit optimally from radiotherapy because of radio‐resistance. Therefore, identifying radio‐resistance biomarkers and unravelling the underlying mechanisms is of critical importance for these patients. In the present study, we found significant upregulation of hepatocyte nuclear factor 1‐alpha (HNF1α) expression in radio‐resistant cervical cancer tissues and cell lines. Depletion of HNF1α reduced and overexpression of HNF1α promoted the resistance of CC cells to irradiation in vitro and in vivo. HNF1α positively regulated DNA repair protein RAD51 homologue 4 (RAD51D) at the protein level but not at the mRNA level. Mechanistically, upregulation of HNF1α enhanced YTH domain‐containing family protein 3 (YTHDF3) transcription, which in turn promoted RAD51D mRNA N6‐methyladenosine (m6A) modification. YTHDF3 mediates HNF1α regulation of cervical cancer radio‐resistance by promoting RAD51D translation in an m6A‐dependent manner. The HFN1α/YTHDF3/RAD51D regulatory axis was found to play a critical role in conferring radio‐resistance of CC cells. In conclusion, dysregulation of the HFN1α/YTHDF3/RAD51D axis may promote the radio‐resistance of CC cells. Blocking this pathway may provide therapeutic benefits against CC radio‐resistance.

BackgroundThis study was designed to explore the effect of menopausal hormone therapy (MHT) on bone mineral density (BMD) in Chinese women.Material/MethodsThis was a prospective, open-label, randomized-controlled clinical trial. We randomly assigned 123 postmenopausal women to 3 groups: group A received 0.625 mg conjugated equine estrogen (CEE) plus 100 mg micronized progesterone (MP), group B received 0.3 mg CEE daily plus 100 mg MP, and group C received 0.625 mg CEE daily plus 10 mg dydrogesterone (DHG). All subjects received a 2-year intervention and drugs were given in a continuous sequential pattern.ResultsNinety-six patients were followed up. At 1 year, groups A and B gained 2.31% and 1.95% BMD, respectively (P<0.01); at 2 years, groups B and C gained 2.37% and 4.15% BMD (P<0.01) respectively. At 2 years, group A gained 3.28% BMD in the femoral neck and 3.77% BMD in Ward’s triangle (P<0.05). At 1 year, group B lost 2.14% BMD in the trochanter and 1.20% BMD in the total hip (P<0.05); at 2 years, group B lost 1.51% BMD in the total hip (P<0.01). ALP, Ca, P, and Ca/Cr levels were all decreased in the 3 groups (P<0.05). The changes in Cr level at 1 and 2 years were not significant when compared with baseline in all groups (P>0.05).ConclusionsBoth lower-dose and standard-dose CEE increased lumbar BMD, sustain femoral neck BMD, and Ward’s triangle BMD, while there was a reduced bone turnover rate. Standard-dose CEE combined with MP can increase BMD at these 2 sites. CEE combined with MP is recommended because it has better clinical benefits.

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