Role of Hydroxysteroid Dehydrogenase-Like 2 (HSDL2) in Human Ovarian Cancer

Abstract

BackgroundOvarian cancer is a common type of malignant neoplasm. Its prognosis is poor because the disease is not well understood. Abnormal lipometabolism in peroxisomes is involved in tumor progression and hydroxysteroid dehydrogenase-like 2 (HSDL2), localized in peroxisomes, might be a regulatory factor in lipometabolism. However, the role of HSDL2 in ovarian cancer progression remains unknown.Material/MethodsHSDL2 expression was detected by qPCR and immunohistochemistry in ovarian tumor samples and qPCR in human ovarian cancer cell lines. Cell proliferation was measured by Celigo and MTT assay. Cell cycle distribution and apoptosis were determined using flow cytometry. Giemsa staining was used for analyzing colony formation. Cell motility was performed using Transwell migration and invasion assays. Tumorigenesis in nude mice was also detected.ResultsHSDL2 expression was upregulated in human ovarian cancer samples and in 3 human ovarian cancer cell lines: SKOV3, HO8910, and OVCAR-3. Higher expression of HSDL2 in ovarian tumor samples was associated with more progressed tumors (P=0.03) and lymphatic metastases (P=0.03). HSDL2 down-regulation by lentiviral-mediated HSDL2 knockdown suppressed cell proliferation, colony formation, and cell motility, while it promoted cell apoptosis and resulted in cell cycle arrest at the G0/G1 phase in human ovarian cancer cell lines OVCAR-3 and SKOV3. HSDL2 knockdown also inhibited tumorigenesis in mouse models.ConclusionsThis study shows that HSDL2 upregulation is associated with ovarian cancer progression. HSDL2 knockdown inhibited cell proliferation, colony formation, motility, and tumorigenesis. It induced apoptosis and cell cycle arrest and might therefore serve as a potential target for ovarian cancer therapy.

The peroxisome: an update on mysteries 2.0

“…After observing an increase in HMG-CoA reductase as well as cholesterol and triglyceride levels in the cultures, the authors hypothesized that peroxisomal β-oxidation under hypoxic conditions might be used to produce acetyl-CoA as a substrate for de novo lipid synthesis. Another recently identified peroxisomal protein, HSDL2 (hydroxysteroid dehydrogenase-like 2) also appears to be up-regulated in glioblastomas (Ruokun et al 2016 ) and ovarian cancer (Sun et al 2018 ). Knockdown of HSDL2 resulted in decreased growth rates in glioblastoma cell lines, and inhibited cell proliferation, colony formation, motility, and tumorigenesis in ovarian cancer cells underlining an important role for peroxisomes in these tumor types.…”

Exonuclease 1 (Exo1) Participates in Mammalian Non-Homologous End Joining and Contributes to Drug Resistance in Ovarian Cancer

“…Despite decreased mortality from ovarian cancer by 21.7% and 2.2% in younger women and elderly woman, respectively. Late stage diagnosis and relapse after surgical followed by platinum chemotherapy still contribute to low survival rate with advanced stage ovarian cancer [2][3][4]. Therefore, more in depth understanding of ovarian cancer treatment resistance and developing new chemotherapy strategies are needed to benefit the patients.…”

Silencing of keratin 17 by lentivirus‑mediated short hairpin RNA inhibits the proliferation of PANC‑1 human pancreatic cancer cells

“…All animals were kept in an SPF animal room at 37˚C and 60-70% humidity, with a 12-h light/dark cycle and free access to food and water. Tumorigenesis was assessed using nude mice as previously described(39). PANC-1 cells (1x10 5 cells in 200 µl PBS per mouse) transfected with KRT17-shRNA-1 or Scr-shRNA lentivector were injected subcutaneously or below the armpit into female BALB/c mice (4-weeks old).…”