Expression of Beclin 1 and LC3 in FIGO stage I–II cervical squamous cell carcinoma and relationship to survival

Zhu, Weipei; Pan, Xiaohong; Li, Feng; Zhang, Yongshen; Lu, Xiao‐Jie

doi:10.1007/s13277-012-0421-4

Cited by 35 publications

(29 citation statements)

References 24 publications

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“…No significant correlation was identified between the expression of Beclin-1 and LC3B and age, pathological grade, tumor depth, lymph node metastasis, or TNM stage of patients with cervical SCC. Although Beclin-1 and LC3 were not found to be associated with age, FIGO stage, pathological differentiation or lymph node metastasis, they may exhibit prognostic significance in early stage cervical SCC (28). Similar results from previous studies have revealed that the expression of Beclin-1 and LC3B in lung cancer tissues was not affected by patient age, gender, smoking, histological type, lymph node metastasis or TNM stage (25).…”

Section: Discussionmentioning

confidence: 94%

Reduced expression of autophagy markers correlates with high-risk human papillomavirus infection in human cervical squamous cell carcinoma

Wang

Yang

Huang³

et al. 2014

Oncology Letters

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Infection by an oncogenic human papillomavirus (HPV), in particular HPV16 and 18, is a high risk factor for developing cervical cancer; however, viral infection alone is not sufficient for cancer progression. Autophagy is hypothesized to be an important process during carcinogenesis. The aim of the present study was to investigate the association between autophagy and high-risk HPV (hrHPV) infection in human cervical squamous cell carcinomas (SCCs), and to analyze the clinical significance of this association. Quantum dot (QD)-based immunofluorescence histochemistry was used to detect the expression of autophagy markers, Beclin-1 and microtubule-associated proteins 1A/1B light chain 3B (LC3B) proteins, in 104 cases of cervical cancer (including 80 SCCs and 24 adenocarcinomas) and 20 normal cervical tissues. hrHPV (HPV16/18) infection was detected by QDs based fluorescence in situ hybridization in cervical cancers. The results revealed that the expression levels of Beclin-1 and LC3B were significantly lower in cervical cancer cells when compared with those of normal cervical squamous epithelial cells, and were found to negatively correlate with hrHPV infection. The expression levels of Beclin-1 and LC3B were not associated with age, tumor grade, tumor stage, tumor node metastasis stage or lymph node metastasis. However, a positive correlation was identified between Beclin-1 and LC3B protein expression. In addition, the absence of autophagy in combination with hrHPV infection may accelerate the progression of cervical SCC. In conclusion, decreased expression of Beclin-1 and LC3B may be important in cervical carcinogenesis. The hrHPV-host cell interaction may inhibit autophagy, which may aid virus duplication and infection, as well as cervical cancer development.

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Section: Discussionmentioning

confidence: 94%

Reduced expression of autophagy markers correlates with high-risk human papillomavirus infection in human cervical squamous cell carcinoma

Wang

Yang

Huang³

et al. 2014

Oncology Letters

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“…HPV16 early genes negatively impact autophagy [69], and in particular the contribution of HPV16 E5 protein has been recently described [70]. Additionally, inhibition of host autophagy significantly enhanced HPV infectivity and its tumorigenic potential [71–74], further underlining the notion that HPV turns off autophagy through many different mechanisms to promote its infection cycle. Here we further support these data showing that the main HPV oncoproteins E6/E7, mostly owing to E6 action on p53, contribute to the autophagic pathway impairment during cellular transformation, by selective inhibition of autolysosome formation (Figs 8 and 9 and Fig E in S1 Text).…”

Section: Discussionmentioning

confidence: 99%

Autophagy regulates UBC9 levels during viral-mediated tumorigenesis

et al. 2017

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UBC9, the sole E2-conjugating enzyme required for SUMOylation, is a key regulator of essential cellular functions and, as such, is frequently altered in cancers. Along these lines, we recently reported that its expression gradually increases during early stages of human papillomavirus (HPV)-mediated cervical lesions transformation. However, a better understanding of how UBC9 is exploited by transforming viral oncoproteins is still needed. In the present study, we show that in human samples HPV drives UBC9 up-regulation also in very early steps of head and neck tumorigenesis, pointing to the important role for UBC9 in the HPV-mediated carcinogenic program. Moreover, using HPV-infected pre-cancerous tissues and primary human keratinocytes as the natural host of the virus, we investigate the pathological meaning and the cellular mechanisms responsible for UBC9 de-regulation in an oncoviral context. Our results show that UBC9 overexpression is promoted by transforming viral proteins to increase host cells’ resistance to apoptosis. In addition, ultrastuctural, pharmacological and genetic approaches crucially unveil that UBC9 is physiologically targeted by autophagy in human cells. However, the presence of HPV E6/E7 oncoproteins negatively impacts the autophagic process through selective inhibition of autophagosome-lysosome fusion, finally leading to p53 dependent UBC9 accumulation during viral-induced cellular transformation. Therefore, our study elucidates how UBC9 is manipulated by HPV oncoproteins, details the physiological mechanism by which UBC9 is degraded in cells, and identifies how HPV E6/E7 impact on autophagy. These findings point to UBC9 and autophagy as novel hallmarks of HPV oncogenesis, and open innovative avenues towards the treatment of HPV-related malignancies.

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“…The processing of the mammalian homologue of the yeast Atg8 protein, LC3-I, was analyzed by western blot analysis. During autophagy, LC3-I undergoes cleavage and lipidation to yield LC3-II, and quantitation of the levels of LC3-I and LC3-II in culture provides a good measurement of the degree of autophagy (20). The LC3-II and LC3-I expression level ratio in the DHA and EPA groups was increased compared with the control group.…”

Section: ω-3 Pufas Inhibit the Proliferation Of A549 Cells A549 Cellsmentioning

confidence: 97%

Role of autophagy in the ω-3 long chain polyunsaturated fatty acid-induced death of lung cancer A549 cells

Yao

Wang

et al. 2015

Oncology Letters

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Abstract. The present study identified that ω-3 long chain polyunsaturated fatty acids (ω-3 PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) demonstrate anti-proliferative effects in lung cancer A549 cells. MTS and cytotoxicity assays were conducted to confirm that ω-3 PUFAs induced cell death. Autophagy-associated gene and signaling pathways were also detected. Microtubule-associated protein light chain 3 (LC3) expression was found to be increased subsequent to treatment with DHA and EPA, and the expression of LC3-II was particularly increased. mRFP-GFP-LC3 fluorescence staining and p62 expression levels were used to detect autophagic flux. The present results indicate that DHA and EPA block autophagic flux, suggesting autophagosome accumulation. Subsequent to treatment with DHA and EPA, which interfered with autophagosomes, the expression of Beclin 1 was significantly decreased, while the expression of phosphorylated Akt and phosphorylated mammalian target of rapamycin was significantly increased. Therefore, DHA and EPA exert anti-proliferative effects by inhibiting autophagy in A549 cells, which highlights the potential of DHA and EPA for use in the prevention or treatment of lung cancer. IntroductionLung cancer is the leading cause of cancer-associated mortality worldwide (1), and the five-year survival rate remains extremely poor (2). Overall, ~75-85% of lung cancers cases are non-small cell lung cancer (NSCLC), which includes squamous cell carcinoma, adenocarcinoma and large cell carcinoma. The treatment of lung cancer involves the use of medical therapies such as surgery, radiation, chemotherapy and palliative care (3) in an attempt to successfully treat or reduce the adverse impact of malignant neoplasms originating in lung tissue. Chemotherapeutic agents are the main treatment measures for NSCLC, but the side-effects are usually difficult to tolerate (4).Fish oils are an excellent source of long-chain ω-3 polyunsaturated fatty acids (ω-3 PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Fish oil supplements are increasingly recognized by clinical studies to be useful for the treatment of a variety of human afflictions, including cancer (5). Numerous studies reveal evidence for the capability of ω-3 PUFAs to decrease proliferation, exert a pro-apoptotic effect and inhibit angiogenesis in several in vitro models of colon cancer (6-9).A previous study indicated that DHA and EPA inhibit the proliferation of A549 cells and induce apoptosis, with autophagy also being observed under transmission electron microscopy (10). Autophagy is a type of programmed cell death and it is an important process that is involved in various human pathologies. Previous studies suggest that autophagy is important in the regulation of cancer development and progression and also in determining the response of tumor cells to anticancer therapy (11)(12)(13)(14). Several cell signaling pathways are implicated in regulating autophagy, including the phosphatidyl inositol 3-kinase (PI3K)/Akt/...

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Expression of Beclin 1 and LC3 in FIGO stage I–II cervical squamous cell carcinoma and relationship to survival

Cited by 35 publications

References 24 publications

Reduced expression of autophagy markers correlates with high-risk human papillomavirus infection in human cervical squamous cell carcinoma

Reduced expression of autophagy markers correlates with high-risk human papillomavirus infection in human cervical squamous cell carcinoma

Autophagy regulates UBC9 levels during viral-mediated tumorigenesis

Role of autophagy in the ω-3 long chain polyunsaturated fatty acid-induced death of lung cancer A549 cells

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