microRNA-499a promotes the progression and chemoresistance of cervical cancer cells by targeting SOX6

Chen, Yibing; Song, Yucen; Mi, Yanjun; Jin, Huan; Cao, Jun; Li, Haolong; Liang, Han; Huang, Ting; Zhang, Xiaofei; Ren, Shan; Ma, Qian; Zou, Zhengzhi

doi:10.1007/s10495-019-01588-y

Cited by 49 publications

(27 citation statements)

References 51 publications

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“…Dong et al ( 13 ) demonstrated a suppressive role of miR-217 in the development of CC cells via targeting Rho-associated protein kinase 1 ( 13 ). Chen et al ( 14 ) reported that miR-499a promotes the proliferation, cell cycle progres-sion, colony formation, migration and invasion of CC cells by targeting SRY-box transcription factor 6. In addition, several miRNAs serve as diagnostic biomarkers in patients with CC, such as miR-152 and miR-365 ( 15 , 16 ).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑15a‑5p‑targeting oncogene YAP1 inhibits cell viability and induces cell apoptosis in cervical cancer cells

et al. 2020

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MicroRNAs (miRNAs) have been reported to have important regulatory roles in the progression of several types of cancer, including cervical cancer (CC). However, the biological roles and regulatory mechanisms of miRNAs in CC remain to be fully elucidated. The aim of the present study was to examine the functions of miRNAs in CC and the possible mechanisms. Using a microarray, it was identified that miRNA-15a-5p (miR-15a-5p) was one of the most down-regulated miRNAs in CC tissues compared with adjacent noncancerous tissues. The low expression of miR-15a-5p was observed in CC tumor tissues with distant metastasis and in CC cell lines. In addition, the effects of miR-15a-5p upregulation on cell viability, apoptosis, invasion and migration of CC cells were investigated using CCK-8, flow cytometry, Transwell and wound healing assays, respectively. It was demonstrated that upregulation of miR-15a-5p significantly suppressed the viability, migration and invasion, and promoted the apoptosis of SiHa and C-33A cells. Furthermore, yes-associated protein 1 (YAP1), a well-known oncogene, was confirmed to be directly targeted by miR-15a-5p and was found to be negatively regulated by miR-15a-5p. Further correlation analysis indicated that miR-15a-5p expression was negatively correlated with YAP1 expression in CC tissues. Notably, overexpression of YAP1 abrogated the tumor suppressive effects of miR-15a-5p in CC cells. Taken together, these present findings indicated that the miR-15a-5p/YAP1 axis may provide a novel strategy for the clinical treatment of CC.

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Section: Introductionmentioning

confidence: 99%

MicroRNA‑15a‑5p‑targeting oncogene YAP1 inhibits cell viability and induces cell apoptosis in cervical cancer cells

et al. 2020

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“…Interestingly, our mechanism research suggested the interaction between CENPK and SOX6. SOX6 plays a role as a tumor suppressor gene in a variety of cancers [27][28][29] , including cervical cancer [30] . Moreover, SOX6 is a Wnt/β-catenin pathway inhibitor and p53 pathway activator [31,32] .…”

Section: Discussionmentioning

confidence: 99%

CENPK Interacts with SOX6 to Promote Cervical Cancer Stemness and Chemoresistance Through Wnt and P53 Signaling

Lin

Wang

Liu

et al. 2021

Preprint

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Background Stemness and chemoresistance contribute to cervical cancer recurrence and metastasis. It is meaningful to develop alternative targets for eliminating cancer stem cells (CSCs) properties, suppressing metastasis, and alleviating chemoresistance in cervical cancer. This study clarifies the role of CENPK in cervical cancer stemness and chemoresistance and its clinical significance in cancer progression. Methods Human cervical cancer cell lines, xenografts, and clinical samples were used for expression and functional analysis. CENPK expression in cervical cancer was analyzed by bioinformatics based on a microarray and TCGA database and immunohistochemistry based on 119 paraffin-embedded cervical cancer specimens and 35 paraffin-embedded adjacent normal tissues in a tissue chip. Results CENPK served as an oncogene by promoting CSCs properties, DNA damage repair, epithelial-mesenchymal transition and DNA replication, thus inducing cisplatin/carboplatin resistance, cell metastasis and proliferation in cervical cancer. Intriguingly, targeting CENPK markedly prolonged the survival time of cervical cancer-bearing mice, and improved chemotherapy sensitivity of cervical cancer cells in vivo. CENPK also interacted with tumor suppressor gene SOX6 to activate Wnt signaling and inactivate p53 signaling. CENPK modulated expression of key regulators in CSCs properties, DNA damage repair, epithelial-mesenchymal transition and DNA replication by disrupting SOX6-β-catenin interaction, promoting β-catenin expression and nuclear translocation, and facilitating SOX6-mediated p53 ubiquitination and nuclear export, thus stimulating cervical cancer stemness, chemoresistance, metastasis and proliferation by. Interestingly, the RAD21/SMC3 complex, downstream targets of β-catenin, enhanced CENPK transcription to form a positive regulatory circuit through Wnt signaling. Facilitation of Wnt signaling by iRhom2 further activated the CENPK/SOX6-β-catenin-RAD21/SMC3 loop and conferred cervical cancer progression, suggesting a Wnt-p53 pathway crosstalk. Importantly, CENPK was upregulated in cervical cancer, correlated with cancer recurrence, and independently predicted poor patient prognosis. Conclusions This work identifies CENPK as a prognostic indicator and highlights targeting of CENPK as a novel strategy in the treatment of cervical cancer.

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“…Major limitations include the absence of studies implementing computational models to identify these miRNAs, technical issues associated with conventional miRNA extraction and detection tools, and scarcity of anal cancer in vitro and in vivo models. Ongoing studies are still being conducted to study miRNA profiles during HIV[ 125 - 127 ] and HPV[ 128 - 130 ] infections. With the appropriate application of advanced bioinformatic analysis tools and computational models, the identification of the most predictive miRNAs, even from complex datasets would be possible.…”

Section: Limitations and Considerations For The Use Of Mirnas As Biomarkers For Anal Cancer Screeningmentioning

confidence: 99%

Potential role of micro ribonucleic acids in screening for anal cancer in human papilloma virus and human immunodeficiency virus related malignancies

Bitar¹,

Doughan²,

Gali‐Muhtasib³

et al. 2021

WJGP

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Despite advances in antiretroviral treatment (ART), human immunodeficiency virus (HIV) continues to be a major global public health issue owing to the increased mortality rates related to the prevalent oncogenic viruses among people living with HIV (PLWH). Human papillomavirus (HPV) is the most common sexually transmitted viral disease in both men and women worldwide. High-risk or oncogenic HPV types are associated with the development of HPV-related malignancies, including cervical, penile, and anal cancer, in addition to oral cancers. The incidence of anal squamous cell cancers is increasing among PLWH, necessitating the need for reliable screening methods in this population at risk. In fact, the currently used screening methods, including the Pap smear, are invasive and are neither sensitive nor specific. Investigators are interested in circulatory and tissue micro ribonucleic acids (miRNAs), as these small non-coding RNAs are ideal biomarkers for early detection and prognosis of cancer. Multiple miRNAs are deregulated during HIV and HPV infection and their deregulation contributes to the pathogenesis of disease. Here, we will review the molecular basis of HIV and HPV co-infections and focus on the pathogenesis and epidemiology of anal cancer in PLWH. The limitations of screening for anal cancer and the need for a reliable screening program that involves specific miRNAs with diagnostic and therapeutic values is also discussed.

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microRNA-499a promotes the progression and chemoresistance of cervical cancer cells by targeting SOX6

Cited by 49 publications

References 51 publications

MicroRNA‑15a‑5p‑targeting oncogene YAP1 inhibits cell viability and induces cell apoptosis in cervical cancer cells

MicroRNA‑15a‑5p‑targeting oncogene YAP1 inhibits cell viability and induces cell apoptosis in cervical cancer cells

CENPK Interacts with SOX6 to Promote Cervical Cancer Stemness and Chemoresistance Through Wnt and P53 Signaling

Potential role of micro ribonucleic acids in screening for anal cancer in human papilloma virus and human immunodeficiency virus related malignancies

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