Rab31 promotes the invasion and metastasis of cervical cancer cells by inhibiting MAPK6 degradation

Huang, Yujie; Liu, Ruijuan; Han, Xuechao; Hou, Xiaoyan; Tian, Yonghao; Zhang, Weifang

doi:10.7150/ijbs.63388

Cited by 18 publications

(14 citation statements)

References 36 publications

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“…Metastasis and cervical cancer invasion are complex processes [ 2 ]. For example, HPV-16 E6 oncoprotein, following a decrease in Na + /H + exchanger regulatory factor 1 (NHERF1), increases ACTN4 actin cytoskeletal protein level and subsequently enhances actin polymerization, migration, and invasion of cervical cancer cells [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…In 1983, Harald Zur Hausen et al first showed the link between human papillomaviruses (HPV) and related cancers, especially cervical cancer [ 1 ]. Cervical cancer is the fourth most common cancer in women; in 2020, it accounted for about 342,000 deaths and 604,000 new cases [ 2 ]. Moreover, according to the World Cancer Reports, the development of cervical cancer is caused by persistent infection of epithelial cells with one or more types of HPV, leading to precancerous lesions and resulting in cervical malignancy [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

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siRNA-E6 sensitizes HPV-16-related cervical cancer through Oxaliplatin: an in vitro study on anti-cancer combination therapy

et al. 2023

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Background Persistent infection with high-risk Human papillomaviruses (HPV), such as hr-HPV-16 and hr-HPV-18, lead to cervical cancer, the fourth most common cancer in the world. In the present study, we investigated the alteration of E6 oncogene expression by E6-specific short interfering RNA (siRNA) combined with Oxaliplatin. Methods The cervical cancer cell line, CaSki, was transfected with E6-siRNA, then treated with Oxaliplatin. The cellular genes, such as p53, MMP9, Nanog, and caspases expression, were assessed by quantitative real-time PCR. The cell death rate, cell cycle, and cell viability were assessed by Annexin V/PI staining, DAPI staining, and MTT test, respectively. Furthermore, colony formation assay and scratch test determined the stemness ability and cell metastasis, respectively. Results Combination therapy increased the re-expression of genes involved in the p53-dependent apoptosis pathway (increase in apoptosis to 44.2%), and reduced stemness and metastasis ability compared to either siRNA or Oxaliplatin monotherapy. Together, our results demonstrate that E6-siRNA and Oxaliplatin combination increased the cervical cancer cells’ sensitivity to Oxaliplatin and decreased the survival rate, proliferation, and metastasis, and consequently escalated apoptosis rate, induced cell cycle arrest in the sub-G1 stage, and reduced the chemotherapy drug dosage. Conclusion Inhibition of E6 oncogene expression and subsequent E6-siRNA with Oxaliplatin combination therapy could be a novel strategy for cervical cancer treatment. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

siRNA-E6 sensitizes HPV-16-related cervical cancer through Oxaliplatin: an in vitro study on anti-cancer combination therapy

et al. 2023

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“…The data was presented in Additional file 3: Table S3. The eight target proteins related biological functions or etiology in multiple tumors according to previous literature's reported [12][13][14][15][16][17][18][19][20][21][22][23][24] (partial) are shown in Table 4. On the other hand, the eight proteins involved the mainly KEGG pathways which those may associated with the etiology of CSCC development in our proteomics results are shown in Table 5.…”

Section: Data Sources and Crosstalk Analysismentioning

confidence: 99%

“…RAB31 belongs to the Rab family, mainly localized in the trans-Golgi network and endosomes, which is the largest Ras superfamily of small molecule GTP binding proteins. Accumulating reports has indicated that RAB31 is widely involved in the prognosis of various cancers, including pancreatic cancer [22], cervical cancer [23] and others. Higher expression of RAB31 was significant associated with shorter overall survival in pancreatic cancer [22] and RAB31 knockdown could inhibited the epithelial-mesenchymal transition and cytoskeletal rearrangement in cervical cancer cells [23].…”

Section: Protein Accessionmentioning

confidence: 99%

“…Accumulating reports has indicated that RAB31 is widely involved in the prognosis of various cancers, including pancreatic cancer [22], cervical cancer [23] and others. Higher expression of RAB31 was significant associated with shorter overall survival in pancreatic cancer [22] and RAB31 knockdown could inhibited the epithelial-mesenchymal transition and cytoskeletal rearrangement in cervical cancer cells [23]. However, little is known regarding the RAB31 expression levels in CSCC.…”

Section: Protein Accessionmentioning

confidence: 99%

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From Bowen disease to cutaneous squamous cell carcinoma: eight markers were verified from transcriptomic and proteomic analyses

et al. 2022

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Background Bowen's disease is a cutaneous squamous cell carcinoma (CSCC) in situ. If left untreated, BD may progress to invasive CSCC. CSCC is one of the most common cutaneous carcinoma in the elderly and the advanced, metastasis CSCC usually have a poor outcomes. However, the mechanisms of invasion and metastasis from Bowen’s disease to CSCC is complicated and still unclear. Objectives The aim of this study was to explore the biomarkers and molecular alterations in Bowen’s disease development process via analyzing the proteomics changes in tissues of CSCC, Bowen disease and healthy skin. Methods A total of 7 individuals with CSCC (5 for proteomics study and 2 for validation), 7 individuals with Bowen disease (5 for proteomics study and 2 for validation) and 7 healthy controls (5 for proteomics study and 2 for validation) presented to the Department of Dermatology, Yijishan Hospital, the First Affiliated Hospital of Wannan Medical College between January 2021 and December 2021 were enrolled. The proteomics analysis was performed to screen differentially expressed proteins/gens (DEPs/DEGs) in the lesions of CSCC, Bowen disease and healthy skin tissues. The transcriptomic data (GSE32628) of CSCC was selected and downloaded from the GEO database. The common DEGs in our proteomics results and GSE32628 between CSCC and healthy skin tissues were selected. And then, the common DEGs which significantly up or down-regulated between CSCC and Bowen disease in our proteomics results were further screened to identify using Western blot methods in the validation group. CSCC A431 cells were transfected with SERPINB1 small interfering RNA (si-SERPINB1) or small interfering RNA negative control (si-NC). To explore the effect of SERPINB1 silencing on migration and invasion ability of A431 cells. Results A total of 501 proteins were differentially expressed between the CSCC and healthy skin tissues, with 332 up-regulated and 169 down-regulated at least 1.5-fold with a P value < 0.05. These DEPs involved multiple biological functions such as protein binding process, immune, inflammation, ribosome, protein digestion and absorption, ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway and others. A total of 20 common DEGs (COL3A1, LUM, TNC, COL1A1, ALDH3A2, FSCN1, SERPINB4, SERPINB1, CD36, COL4A1, CSTB, GPX3, S100A7, ACTN1, SERPINB3, S100A8, RAB31, STAT1, SPRR1B, S100A9) between CSCC and healthy skin tissues in GSE32628 and our proteomics results were found. Besides, the proteins of TNC, FSCN1, SERPINB1, ACTN1 and RAB31 in CSCC were significantly up-regulated, while COL3A1, COL1A1 and CD36 were significantly down-regulated relative to Bowen disease in proteomics results. These proteins were mainly involved in multiple pathways, including Focal adhesion, ECM-receptor interaction, Human papillomavirus infection, PI3K-Akt signaling pathway, PPAR signaling pathway, AMPK signaling pathway and others. These eight proteins were selected for further validation. According to the Western blotting analysis, when compared with the Bowen disease and healthy skin tissues, we found that the relative expression levels of TNC, FSCN1, SERPINB1, ACTN1 and RAB31 in the CSCC were significantly increased, while COL1A1 and CD36 were significantly decreased, and the differences were statistically significant (P < 0.05). Furthermore, the relative expression levels of TNC, FSCN1, SERPINB1 in the Bowen disease were also significantly increased, while the COL3A1 were also significantly decreased relative to the healthy control. SERPINB1 siRNA inhibited the expression of SERPINB1 at mRNA and protein levels in the A431 cells. After interfering with the expression of SERPINB1, the migration and invasion ability in the A431 cells were significantly decreased (P < 0.05). Conclusions This study highlights that eight proteins, TNC, FSCN1, SERPINB1, ACTN1, RAB31, COL3A1, COL1A1, CD36, were significantly associated with the mechanisms of invasion and metastasis in Bowen’s disease.

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RAB31 drives extracellular vesicle fusion and cancer‐associated fibroblast formation leading to oxaliplatin resistance in colorectal cancer

Chang,

Yang,

et al. 2024

J of Extracellular Bio

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Epithelial‐mesenchymal transition (EMT) is associated with tumorigenesis and drug resistance. The Rab superfamily of small G‐proteins plays a role in regulating cell cytoskeleton and vesicle transport. However, it is not yet clear how the Rab family contributes to cancer progression by participating in EMT. By analysing various in silico datasets, we identified a statistically significant increase in RAB31 expression in the oxaliplatin‐resistant group compared to that in the parental or other chemotherapy drug groups. Our findings highlight RAB31's powerful effect on colorectal cancer cell lines when compared with other family members. In a study that analysed multiple online meta‐databases, RAB31 RNA levels were continually detected in colorectal tissue arrays. Additionally, RAB31 protein levels were correlated with various clinical parameters in clinical databases and were associated with negative prognoses for patients. RAB31 expression levels in all three probes were calculated using a computer algorithm and were found to be positively correlated with EMT scores. The expression of the epithelial‐type marker CDH1 was suppressed in RAB31 overexpression models, whereas the expression of the mesenchymal‐type markers SNAI1 and SNAI2 increased. Notably, RAB31‐induced EMT and drug resistance are dependent on extracellular vesicle (EV) secretion. Interactome analysis confirmed that RAB31/AGR2 axis‐mediated exocytosis was responsible for maintaining colorectal cell resistance to oxaliplatin. Our study concluded that RAB31 alters the sensitivity of oxaliplatin, a supplementary chemotherapy approach, and is an independent prognostic factor that can be used in the treatment of colorectal cancer.

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Rab31 promotes the invasion and metastasis of cervical cancer cells by inhibiting MAPK6 degradation

Cited by 18 publications

References 36 publications

siRNA-E6 sensitizes HPV-16-related cervical cancer through Oxaliplatin: an in vitro study on anti-cancer combination therapy

siRNA-E6 sensitizes HPV-16-related cervical cancer through Oxaliplatin: an in vitro study on anti-cancer combination therapy

From Bowen disease to cutaneous squamous cell carcinoma: eight markers were verified from transcriptomic and proteomic analyses

RAB31 drives extracellular vesicle fusion and cancer‐associated fibroblast formation leading to oxaliplatin resistance in colorectal cancer

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