Mitochondrial DNA copy number in cervical exfoliated cells and risk of cervical cancer among HPV-positive women

Sun, Wei; Qin, Xueyun; Zhou, Jing; Xu, Mingjing; Lyu, Zhangyan; Li, Xin; Zhang, Kai; Dai, Min; Ni, Li; Hang, Dong

doi:10.1186/s12905-020-01001-w

Cited by 13 publications

(17 citation statements)

References 48 publications

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“…In humans, dysregulation of mitochondria's structure and function is linked with all stages of cancer progression. Additionally, studies have reported the association between pathogenic mtDNA variations with CC (Sun et al, 2020). Moreover, mitochondrial defects can promote tumor growth and metastasis by providing energy to growing cancer cells, promoting cell survival via activation of anti-apoptotic signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

“…Defects in both structure and function of mitochondria contribute to resistance to apoptosis, abnormal cell proliferation, and therapy resistance in cancer (Indran et al, 2011). Both somatic mutation and mtDNA copy number changes are linked with cancer, including CC (Chatterjee et al, 2006;Sun et al, 2020). Although mtDNA encodes for proteins, most of the protein required for its function is synthesized by nuclearencoded genes.…”

Section: Introductionmentioning

confidence: 99%

“…The anterograde and retrograde signaling between mitochondria and the nucleus is critical for the normal functioning of the cell (Pfanner et al, 2019). Many nuclear-encoded genes linked with mitochondrial function (NEMG) show a significant difference in their expression in normal and CC conditions (Sun et al, 2020). Therefore, profiling the expression of NEMG can be useful as a sensitive and specific biomarker for diagnostic and prognostic applications in CC.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of Nuclear Encoded Mitochondrial Gene Networks in Cervical Cancer

Meneur

Eswaran

Adiga

et al. 2021

Asian Pac J Cancer Prev

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Cervical cancer (CC) is a significant public health problem affecting women in countries with low resource settings. According to the Global Cancer Observatory database, there were 570,000 cases and 311,000 deaths due to CC in 2018 (Ferlay et al., 2018). Over a third of the overall global CC cases were contributed together by India and China. In 2018, the CC cases in India and China were 97,000 and 106,000, respectively, with mortality of 60,000 and 48,000, respectively (Arbyn et al., 2020;Bray et al., 2018). The Squamous cell carcinoma (SCC) is the most common CC histological type. The standard method for CC treatment includes surgery, chemotherapy, and radiotherapy. Persistent infection with high-risk HPV, high parity, multiple sexual partners, smoking cigarettes,

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Analysis of Nuclear Encoded Mitochondrial Gene Networks in Cervical Cancer

Meneur

Eswaran

Adiga

et al. 2021

Asian Pac J Cancer Prev

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“…Based on the measurement of mtDNA levels in the tested samples, we concluded that mitochondria are the most numerous in the HSIL+ and SCC+ groups, and the least in LSIL− and LSIL+ ( Figure 5 ). Previously it was reported that an increase in the mitochondrial genome copy number in cervical epithelial cells is associated with dysplasia and oncogenesis [ 36 , 66 ]. The obtained results correlate with the amount of lipids in the cytoplasm and inversely correlate with methylation of the SREBF1 gene ( Figure 2 A and Figure 4 A,B).…”

Section: Discussionmentioning

confidence: 99%

Dual Switch in Lipid Metabolism in Cervical Epithelial Cells during Dysplasia Development Observed Using Raman Microscopy and Molecular Methods

Sitarz

Czamara

Bialecka³

et al. 2021

Cancers

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Cellular lipid metabolism is significantly transformed during oncogenesis. To assess how dysplasia development influences lipid cellular metabolisms and what is the molecular background behind it, cervical epithelial cells of 63 patients assigned to seven groups (based on the cytological examination and HPVhr test results) were studied using a multimethodological approach including Raman microscopy and molecular methods. The consistent picture obtained studying the lipid content, cell inflammation, SREBF1 gene methylation (hence SREBP1 inhibition) and level of mitochondrial DNA copies (indirectly the number of mitochondria) showed that changes in lipid metabolism were multidirectional. Cells from patients classified as mildly dysplastic (LSIL) exhibited a unique behavior (the highest level of inflammation and SREBF1 methylation, the lowest lipid content and mitochondrial DNA). On the contrary, cells from severe dysplastic (HSIL) and cancer (SCC) groups showed the opposite characteristics including the lowest SREBF1 gene methylation as well as the highest level of mitochondrial DNA and lipid cellular concentration (for HSIL/HPVhr+ and SCC groups). Following dysplastic progression, the lipid content decreases significantly (compared to the control) for mildly abnormal cells, but then increases for HSIL/HPVhr+ and SCC groups. This intriguing dual switch in lipid metabolism (reflected also in other studied parameters) on the way from normal to squamous carcinoma cells is of potential diagnostic interest.

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“…HPV-related cancers display several degrees of alteration in the mitochondrial metabolism; however, all are dependent on the metabolism of the mitochondria, both for completing their energy metabolism and for avoiding cell death [ 54 , 75 , 76 , 77 ]. Because of these roles, the mitochondria are an attractive target for HPV-related cancer therapy, even at early stages such as during HPV infection.…”

Section: Mitochondrial Therapy In Hpv-related Cancersmentioning

confidence: 99%

Targeting Mitochondrial Therapy in the Regulation of HPV Infection and HPV-Related Cancers

et al. 2023

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It has been previously proposed that some types of cancer cells reprogram their metabolic pathways, favoring the metabolism of glucose by aerobic glycolysis (Warburg effect) instead of oxidative phosphorylation, mainly because the mitochondria of these cells are damaged, thus displaying mitochondrial dysfunction. However, in several cancers, the mitochondria do not exhibit any dysfunction and are also necessary for the tumor’s growth and maintenance. Remarkably, if the mitochondria are dysfunctional, specific processes associated with the release of cytochrome c (cyt c), such as apoptosis, are significantly impaired. In these cases, cellular biotherapies such as mitochondrial transplantation could restore the intrinsic apoptotic processes necessary for the elimination of cancers. On the other hand, if the mitochondria are in good shape, drugs that target the mitochondria are a valid option for treating the related cancers. Famously, the mitochondria are targeted by the human papillomavirus (HPV), and HPV-related cancers depend on the host’s mitochondria for their development and progression. On the other hand, the mitochondria are also important during treatment, such as chemotherapy, since they are key organelles for the increase in reactive oxygen species (ROS), which significantly increases cell death due to the presence of oxidative stress (OS). In this way, the mitochondria in HPV infection and in the development of HPV-related cancer could be targeted to reduce or eliminate HPV infections or HPV-related cancers. To our knowledge, there was no previous review specifically focusing on this topic, so this work aimed to summarize for the first time the potential use of mitochondria-targeting drugs, providing molecular insights on the main therapeutics developed so far in HPV infection and HPV-related cancer. Thus, we reviewed the mechanisms associated with HPV-related cancers, with their early proteins and mitochondrial apoptosis specifically induced by different compounds or drugs, in which these molecules induce the production of ROS, the activation of proapoptotic proteins, the deactivation of antiapoptotic proteins, the loss of mitochondrial membrane potential (Δψm), cyt c release, and the activation of caspases, which are all events which lead to the activation of mitochondrial apoptosis pathways. This makes these compounds and drugs potential anticancer therapeutics that target the mitochondria and could be exploited in future biomedical strategies.

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Mitochondrial DNA copy number in cervical exfoliated cells and risk of cervical cancer among HPV-positive women

Cited by 13 publications

References 48 publications

Analysis of Nuclear Encoded Mitochondrial Gene Networks in Cervical Cancer

Analysis of Nuclear Encoded Mitochondrial Gene Networks in Cervical Cancer

Dual Switch in Lipid Metabolism in Cervical Epithelial Cells during Dysplasia Development Observed Using Raman Microscopy and Molecular Methods

Targeting Mitochondrial Therapy in the Regulation of HPV Infection and HPV-Related Cancers

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