Estrogen-related receptor beta (ERRβ) is downregulated in breast cancer cells and its overexpression in breast cancer patients is positively correlated with an improved prognosis and prolonged relapse-free survival. Here, we unravelled a molecular mechanism for ERRβ downregulation in breast cancer. We found that ERRβ is a key substrate of the SCF complex and that NEDDylation can activate the Cullin subunits of the SCF complex to target ERRβ for degradation in breast cancer. Consistently, using in vitro and in vivo models, we demonstrated that MLN4924, a specific small molecule inhibitor of NEDDylation, can restore ERRβ expression and culminate in a reduction in cell proliferation and migration of breast cancer cells. We also showed that increased ERRβ expression promotes the upregulation of its target genes, including the tumour suppressors p21 Cip1/Waf1 and E-cadherin, involved in cell proliferation and migration arrest at the gene promoter level. Interestingly, this tumour suppressive role of ERRβ does not depend on the expression of ERα in breast cancer. Moreover, our data revealed that the ERRβ recruits the transcription co-activator p300 to its targeted gene promoters to upregulate their expression. Collectively, our work revealed that restoration of ERRβ expression using the NEDDylation inhibitor MLN4924 can be a novel and effective strategy for breast cancer treatment.

Highlights Estimated prevalence of perinatal depression in rural Bihar, India was 23.9%. Perinatal depression is associated with mother’s physical illness and previous abortions. Poor financial status and ill-treatment by in-laws predicted perinatal depression.

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Pregnancy in a non-communicating rudimentary horn is rare and the outcome almost always unfavorable, usually ending in rupture during the first or second trimester with significant morbidity and mortality. Despite the availability and advances on imagiologic procedures, recognition of this ectopic pregnancy is frequently made at laparotomy after abdominal pain and collapse. Full term pregnancy in rudimentary horn is rarely reported. We report a case of full term unruptured intrauterine pregnancy of a dead fetus in a non-communicating horn in a multigravida 37 weeks 4 days which was diagnosed pre-operatively as dead intra-abdominal pregnancy The diagnosis was missed by prenatal ultrasonography and was made only at laparotomy. Extraction of intrauterine dead fetus weighting 3kg with excision of non-communicating rudimentary horn was carried out. In the literature, few reports of a horn pregnancy reaching the viability of full term are described, enhancing the clinical importance of this case.

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