Loss of autophagy-related protein Beclin 1 may define poor prognosis in ovarian clear cell carcinomas

Katagiri, Hiroshi; Nakayama, Kentaro; Sultana, Rehena; Nakamura, Kazuto; Sato, Emi; Ishibashi, Tatsuro; Ishikawa, Masatoshi; Iida, Kouji; Ishikawa, Noriyoshi; Otsuki, Yoshiro; Nakayama, Shinichi; Kyo, Satoru

doi:10.3892/ijo.2015.3191

Cited by 23 publications

(24 citation statements)

References 35 publications

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“…Autophagy is related to a variety of autophagy-related genes, among which LC3 and Beclin1 are important autophagic factors (15). LC3, as a homologous gene with autophagy-related gene Atg8 in yeast, and a specific marker of autophagosome, which expression level can directly reflect the level of autophagy (16).…”

Section: Discussionmentioning

confidence: 99%

Expression and significance of autophagy genes LC3, Beclin1 and MMP-2 in endometriosis

Sui

Sun

et al. 2018

Exp Ther Med

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Expression of autophagy-related proteins, microtubule-associated protein light chain 3 (LC3) and Beclin1, and matrix metalloproteinase-2 (MMP-2) was investigated in serum and peritoneal fluid of patients with endometriosis (EM). The messenger ribonucleic acid (mRNA) expression levels of MMP-2, LC3 and Beclin1 in endometrial tissues of EM patients and correlation of these genes with EM and their significance were evaluated. The serum, peritoneal fluid and endometrial tissues of 84 patients treated in The First Affiliated Hospital of Qiqihar Medical University (Qiqihar, China) from March 2016 to March 2017 were collected. The serum, peritoneal fluid and endometrial tissues of 42 EM patients were used as the experimental group, while those of 42 non-EM patients were used as the control group. The levels of LC3, Beclin1 and MMP-2 in serum and peritoneal fluid of EM patients and non-EM patients were quantitatively detected via enzyme-linked immunosorbent assay (ELISA), followed by comparative analysis based on data in both groups. In addition, mRNA expression of LC3, Beclin1 and MMP-2 in the endometrium in both groups were detected via reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and differences in expression of these genes between the groups were analyzed and evaluated. Correlation of LC3, Beclin1 and MMP-2 with EM was explored. Results of ELISA showed that levels of LC3 and Beclin1 in the EM group were significantly lower than those in the control group, while levels of MMP-2 in serum and peritoneal fluid of the EM group were significantly higher than those in the control group (P<0.05). Results of RT-qPCR revealed that mRNA expression of LC3 and Beclin1 in the endometrium of patients in the EM group were obviously decreased compared with those in the control group, while the expression of MMP-2 was high, and differences in expression were statistically significant (P<0.05). The expression of MMP-2 is high, and expression of LC3 and Beclin1 is low in serum, peritoneal fluid and endometrium of EM patients, and investigating the expression of MMP-2, LC3 and Beclin1 in EM is helpful to further clarify the pathogenesis of EM, and guide the clinical diagnosis and treatment.

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Section: Discussionmentioning

confidence: 99%

Expression and significance of autophagy genes LC3, Beclin1 and MMP-2 in endometriosis

Sui

Sun

et al. 2018

Exp Ther Med

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“… 11 , 12 This type of cell death is defined as type II programmed cell death, or autophagic cell death, and deregulation of this process can lead to changes in cell homeostasis, resulting in tumorigenesis. 13 Therefore, it is essential to determine the underlying molecular mechanisms of autophagy in ovarian cancer, which may be helpful for early detection, diagnosis and treatment.…”

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confidence: 99%

The lncRNA HULC functions as an oncogene by targeting ATG7 and ITGB1 in epithelial ovarian carcinoma

Chen

Sang

et al. 2017

Cell Death Dis

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Highly upregulated in liver cancer (HULC) is a long noncoding RNA (lncRNA), which has recently been identified as a key regulator in the progression of hepatocellular carcinoma, gliomas and gastric cancer. However, its role in epithelial ovarian carcinoma (EOC) remains unknown. In this study, HULC expression was examined in EOC, borderline and benign ovarian tumors, and normal ovarian tissues by RT-PCR. Ovarian cancer cell phenotypes, as well as autophagy-associated proteins were examined after HULC overexpression or downregulation by plasmid or small interfering RNA (siRNA) transfection, respectively. LncRNA–protein interactions were examined by ribonucleoprotein immunoprecipitation (RIP) assays. We found that HULC expression levels were higher in EOC tissues than normal samples. HULC overexpression induced cell proliferation, migration, invasion, whereas reduced cell apoptosis in vitro and induced tumor growth in vivo. In contrast, downregulation of HULC by siRNA transfection reduced cell proliferation, migration and invasion, and induced cell apoptosis and autophagy. Our results showed that HULC overexpression reduced ATG7, LC3-II and LAMP1 expression, while inducing SQSTM1 (P62) and ITGB1 expression. HULC downregulation had the opposite effects. Furthermore, RIP indicated that ATG7 interacted with HULC; ATG7 downregulation also induced cell proliferation, reduced apoptosis and inhibited autophagy in vitro by reducing LC3-II and LAMP1 expression, while inducing SQSTM1 expression. Furthermore, ATG7 co-transfection with HULC reversed the oncogenic effects of HULC both in vitro and in vivo; however, downregulating ATG7 did not affect cell migration and invasive ability. We found that ITGB1 siRNA co-transfection with HULC reversed the function of HULC in inducing ovarian cancer cell migration and invasive ability. Taken together, our results show that HULC may promote ovarian carcinoma tumorigenesis by inhibiting ATG7 and inducing progression by regulating ITGB1.

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“…It was demonstrated that the expression levels of beclin 1, p62 and ATG5 protein in T24 cells were decreased in a dose-dependent manner following treatment with MMC and increasing 5-Aza-CdR concentrations. Beclin 1, p62 and ATG5 are considered as the key regulators of autophagic cell death (14)(15)(16). Autophagy is a lysosome-dependent self-digesting system primarily responsible for the removal and recycling of long-lived proteins, and damaged or obsolete intracellular organelles, in order to maintain cell homeostasis (17).…”

Section: Discussionmentioning

confidence: 99%

Role of 5‑Aza‑CdR in mitomycin‑C chemosensitivity of T24 bladder cancer cells

et al. 2017

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Abstract. Chemotherapeutic insensitivity is one of key obstacles to effectively treating muscle invasive bladder cancer. 5-Aza-2'-deoxycytidine (5-Aza-CdR) has been identified as a tumor suppressive agent in various types of cancer. The aim of the present study was to identify the effects of 5-Aza-CdR on the mitomycin-C (MMC) chemosensitivity of T24 bladder cancer cells and investigate the underlying mechanisms. T24 cells were treated with a combination of MMC and 5-Aza-CdR at various concentrations. The rates of proliferation and apoptosis were assessed by an MTT assay and flow cytometry, respectively. The expression of drug resistance-associated proteins, including P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1), and autophagy-associated proteins, including beclin 1, nucleoporin 62 (p62) and autophagy protein 5 (ATG5) were detected with western blotting. Treatment with 5-Aza-CdR significantly promoted the MMC chemosensitivity of T24 cells. The proliferation of T24 cells was significantly inhibited with increasing 5-Aza-CdR concentration, whereas apoptosis was significantly increased. This was associated with the decreased expression of P-gp, MRP1, beclin 1, p62 and ATG5. In conclusion, 5-Aza-CdR enhanced MMC chemosensitivity in bladder cancer T24 cells, which may be caused by the suppression of drug resistance-and autophagy-associated proteins.

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Loss of autophagy-related protein Beclin 1 may define poor prognosis in ovarian clear cell carcinomas

Cited by 23 publications

References 35 publications

Expression and significance of autophagy genes LC3, Beclin1 and MMP-2 in endometriosis

Expression and significance of autophagy genes LC3, Beclin1 and MMP-2 in endometriosis

The lncRNA HULC functions as an oncogene by targeting ATG7 and ITGB1 in epithelial ovarian carcinoma

Role of 5‑Aza‑CdR in mitomycin‑C chemosensitivity of T24 bladder cancer cells

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