Epithelial ovarian cancer (EOC) is a highly lethal gynecological malignancy, and cisplatin resistance is usually correlated with the poor prognosis of EOC. Increasing evidence indicates that the dysregulation of miRNAs is related to chemotherapy sensitivity. In this study, we revealed that miR-98-5p, a member of the let-7 family, was enriched in cisplatin-resistant EOC cells compared with cisplatin-sensitive cells, and could promote cisplatin resistance in EOC cells. Further studies showed that miR-98-5p could directly target the 3′-UTR of Dicer1 and suppress its expression, causing global miRNA downregulation. By miRNA array and qRT-PCR verification, we identified miR-152 as the vital downstream target of the miR-98-5p/Dicer1 axis in EOC cells. Moreover, we demonstrated that the ectopic expression of miR-152 reversed cisplatin resistance both in vitro and in vivo by targeting RAD51, a central member in homologous recombination. Importantly, miR-98-5p expression, as determined by in situ hybridization in tumor tissues, was associated with poor outcome of EOC patients. Together, these findings suggest the essential role of the miR-98-5p/Dicer1/miR-152 pathway in regulating cisplatin resistance of EOC cells and provide a potential target for EOC therapy.

Anti-CD47/PD-L1 immunotherapies aiming to enhance antitumor immunity are being intensively investigated and show promising results in cancer therapy; however, not all patients treated with these new drugs respond. Thus, developing new immunotherapy agents or combination treatments to enhance the efficacy of immunotherapy is an urgent challenge. Here, we found that LSD1 knockdown directly downregulated the expression of CD47 and PD-L1 through upregulating H3K4me2 levels in the CD47 and CD274 promoter regions. In addition, the LSD1/wild-type p53/miR-34a signaling axis was also involved in the regulation of CD47/PD-L1 expression by targeting the 3′ untranslated regions (3′UTRs) of CD47/PD-L1. Further, the results showed that an LSD1 inhibitor (ORY-1001) combined with anti-CD47/PD-L1 monoclonal antibodies inhibited tumor growth in an established subcutaneous xenograft model more effectively than a single blockade strategy. Collectively, these findings indicate that LSD1 inhibition enhances the therapeutic efficacy of PD-L1/CD47 blockade by reducing CD47 and PD-L1 expression in cervical cancer.

The tumor suppressor menin is recognized as a key regulator of β-cell proliferation. To induce tumorigenesis within the pancreatic β-cells, floxed alleles of Men1 were selectively ablated using Cre-recombinase driven by the insulin promoter. Despite the β-cell specificity of the RipCre, glucagon-expressing tumors as well as insulinomas developed in old mutant mice. These glucagon-expressing tumor cells were menin deficient and expressed the mature α-cell-specific transcription factors Brain-specific homeobox POU domain protein 4 (Brn4) and v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B (MafB). Moreover, the inactivation of β-cell-specific transcription factors was observed in mutant β-cells. Our work shows that Men1 ablation in the pancreatic β-cells leads to the inactivation of specific transcription factors, resulting in glucagon-expressing tumor development, which sheds light on the mechanisms of islet tumorigenesis.

Background: Tubal choriocarcinoma is an extremely rare but highly malignant trophoblastic tumor, which may be either gestational or non-gestational in origin. Due to atypical clinical manifestations and symptoms similar to ectopic pregnancy, it is easily to be confused with ectopic pregnancy. In addition, inadequate understanding of this rare disease by clinicians often leads to misdiagnosis or missed diagnosis, which in turn results in delayed treatment or even tumor metastasis.Case presentation: This report summarized a case of a woman who was finally diagnosed as tubal choriocarcinoma through the follow-up of serum β hCG levels and histopathological results after undergoing salpingectomy for being misdiagnosed as ectopic pregnancy. Five courses of adjuvant chemotherapy (5-fluorouracil, actinomycin-D, vinorelbine regime) have been administered to the patient in the prevention of any recurrences. During 1-year follow-up, the patient was asymptomatic and presented no evidence of recurrence.Conclusions: Tubal choriocarcinoma is easily to be confused with ectopic pregnancy. By analyzing this case and previous related cases, we aimed to provide references for clinicians in the diagnosis and treatment of tubal choriocarcinoma.