The mitochondrial RNA polymerase POLRMT promotes skin squamous cell carcinoma cell growth.

RNA polymerase mitochondrial (POLRMT) expression and the potential biological functions in skin squamous cell carcinoma (SCC) were explored. We showed that POLRMT is significantly elevated in skin SCC. Genetic depletion of POLRMT, using shRNA-induced knockdown or CRISPR/Cas9-mediated knockout (KO), resulted in profound anti-skin SCC cell activity. In patient-derived primary skin SCC cells or immortalized lines (A431 and SCC-9), POLRMT shRNA or KO potently suppressed mitochondrial DNA (mtDNA) transcription and suppressed cell viability, proliferation and migration. POLRMT shRNA or KO impaired mitochondrial functions in different skin SCC cells, leading to production of ROS (reactive oxygen species), depolarization of mitochondria and depletion of ATP. Moreover, mitochondrial apoptosis cascade was induced in POLRMT-depleted skin SCC cells. IMT1, a POLRMT inhibitor, largely inhibited proliferation and migration, while inducing depolarization of mitochondria and apoptosis in primary skin SCC cells. Contrarily, ectopic overexpression of POLRMT increased mtDNA transcription and augmented skin SCC cell growth. Importantly, POLRMT shRNA adeno-associated virus injection robustly hindered growth of the subcutaneous A431 xenografts in mice. In the POLRMT shRNA virus-treated A431 xenograft tissues, POLRMT depletion, mtDNA transcription inhibition, cell apoptosis, lipid peroxidation and ATP depletion were detected. Together, overexpressed POLRMT increases mtDNA transcription and promotes skin SCC growth.

Comprehensive analysis of the differential expression profile of microRNAs in missed abortion.

To screen the key circulating microRNAs (miRNAs) involved in missed abortion (MA) and explore their role in MA process. We examined the miRNA profile from the serum of three MA patients and three early pregnancy induced abortion patients (controls) by next-generation sequencing. We analyzed the target genes of the differentially expressed (DE) miRNAs to analyze the function and pathway enrichment using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, respectively. We validated five candidate miRNAs by real time-qPCR. Integrated miRNA-mRNA-pathway network analysis was performed to show the interaction network of the candidate miRNAs and their target genes of interest with the involved pathways. It was observed that 227 miRNAs were differently expressed between the MA group and the early pregnancy control group, with 58 miRNAs downregulated and 169 miRNAs upregulated in the MA group. Real-time qPCR results revealed that expression of the five candidate miRNAs, namely hsa-miR-22-3p, hsa-miR-145-3p, hsa-miR-107, hsa-miR-361-3p, and hsa-miR-378c, was consistent with the miRNA data obtained by sequencing. Integrated miRNA-mRNA-pathway network analysis illustrated that target genes of the candidate miRNAs were mainly involved in the PI3K-Akt signaling pathway, HIF-1 signaling pathway, and VEGF signaling pathway, which would have potential significance in pregnancy and MA. We are the first to reveal the DE miRNAs involved in MA and illustrate their functional interaction network. These results might provide potential circulating biomarkers and new therapeutic targets for MA.

Effect of vasopressin injection technique in laparoscopic excision of bilateral ovarian endometriomas on ovarian reserve: prospective randomized study.

STUDY OBJECTIVE: To evaluate the effects of vasopressin injection technique in laparoscopic cystectomy on ovarian reserve in patients with bilateral endometriomas. DESIGN: Randomized prospective study (Canadian Task Force classification I). SETTING: University hospital. PATIENTS: Eighty-six women with bilateral endometriomas. INTERVENTIONS: Laparoscopic cystectomy of bilateral endometriomas was performed using different techniques including laparoscopic cystectomy by stripping without injection (control group), laparoscopic cystectomy by stripping with injection of saline solution (saline group), and laparoscopic cystectomy by stripping with vasopressin injection technique (VIT group). MEASUREMENTS AND MAIN RESULTS: The number of coagulation events on the ovarian cortex for hemostasis was counted in different groups, and the thickness of ovarian tissues removed was measured. The basal follicle-stimulating hormone (FSH) level was determined before surgery and at 3-, 6-, and 12-month follow-up after laparoscopic cystectomy in the different groups. In the saline group, fewer coagulation events were required to achieve hemostasis, less ovarian tissues were removed, and lower preoperative FSH levels were detected than in the control group (p < .01). In the VIT group, even fewer coagulation events (p < .01) and lower preoperative FSH levels (p < .01) were detected than in the saline group. There was no significant difference in the thickness of ovarian tissues removed in the 2 groups (p > .05). Basal FSH levels were significantly different before and after surgery in the control and saline groups (p < .01) but not in the VIT group (p > .05). CONCLUSION: Vasopressin injection is an ideal procedure to reduce damage from usual laparoscopic cystectomy of bilateral ovarian endometriomas to protect ovarian reserve.