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Oral Fibrosis and Oral Cancer: From Molecular Targets to Therapeutics 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 16956

Special Issue Editor

Prof. Dr. Cheng-Chia Yu

E-Mail Website
Guest Editor
Institute of Oral Sciences, College of Oral Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
Interests: cancer stemness; microRNAs; long non-coding RNAs; oral submucous fibrosis; oral cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Oral submucous fibrosis (OSF) is a chronic scarring disease that has been considered as a pre-cancerous condition of the oral mucosa with a rate of malignant transformation around 7–13%. Therefore, it is imperative to further decipher the mechanism underlying the pathogenesis of OSF and oral cancer in order to develop better treatment approaches and prevent cancer development. To date, it has been known that OSF is associated with the increased myofibroblast activity and dysregulation of collagen homeostasis. As such, inhibition of myofibroblast activation has been regarded as a potential therapeutic direction for OSF. On the other hand, mounting evidence has shown that chemo/radioresistance and metastasis are due to the existence of cancer stem cells or epithelial-mesenchymal transition (EMT). It has been revealed that various non-coding RNAs are key regulators of cancer stemness and EMT and may also be the critical factors that affect the progression of OSF or oral cancer. Moreover, several natural compounds have been shown to exhibit the capacity to modulate the expression of these non-coding RNAs and may serve as promising adjunct therapies to treat OSF or oral cancer.

In this Special Issue, contributions are encouraged to discuss screening strategies, pathogenesis, molecular targets, and therapeutics options for OSF and oral cancer. It is envisioned that this Special Issue will help readers to become more familiar with cutting-edge advances and may even accelerate the discovery and development of effective treatments for OSF and oral cancer.

Prof. Dr. Cheng-Chia Yu
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • oral submucous fibrosis
  • oral Cancer
  • myofibroblast
  • epithelial-mesenchymal transition
  • natural compounds
  • non-coding RNAs (ncRNAs)
  • miRNAs
  • lncRNAs
  • chemo/radioresistance
  • metastasis

Published Papers (7 papers)

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Editorial

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3 pages, 168 KiB  
Editorial
Oral Fibrosis and Oral Cancer: From Molecular Targets to Therapeutics
by Pei-Ling Hsieh and Cheng-Chia Yu
Int. J. Mol. Sci. 2022, 23(11), 6110; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23116110 - 30 May 2022
Cited by 2 | Viewed by 1579
Abstract
Oral submucous fibrosis (OSF) belongs to a group of potentially malignant disorders that are characterized by the progressive fibrosis of the lining mucosa as well as an increasing loss of tissue mobility [...] Full article
(This article belongs to the Special Issue Oral Fibrosis and Oral Cancer: From Molecular Targets to Therapeutics 2.0)

Research

Jump to: Editorial, Review

13 pages, 2615 KiB  
Article
Real-Time Monitoring of the Cytotoxic and Antimetastatic Properties of Cannabidiol in Human Oral Squamous Cell Carcinoma Cells Using Electric Cell-Substrate Impedance Sensing
by Chien-Chu Huang, Shao-Chih Chiu, Shih-Chi Chao, Heng-Yi Liao, Shiao-Pieng Lee, Chun-Chung Huang and Der-Yang Cho
Int. J. Mol. Sci. 2022, 23(24), 15842; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232415842 - 13 Dec 2022
Viewed by 1599
Abstract
Cannabidiol (CBD) is an active natural compound that is extracted from Cannabis sativa. Previous studies show that CBD is a nonpsychotropic compound with significant anticancer effects. This study determines its cytotoxic effect on oral cancer cells and OEC-M1 cells and compares the [...] Read more.
Cannabidiol (CBD) is an active natural compound that is extracted from Cannabis sativa. Previous studies show that CBD is a nonpsychotropic compound with significant anticancer effects. This study determines its cytotoxic effect on oral cancer cells and OEC-M1 cells and compares the outcomes with a chemotherapeutic drug, cisplatin. This study has investigated the effect of CBD on the viability, apoptosis, morphology, and migration of OEC-M1 cells. Electric cell–substrate impedance sensing (ECIS) is used to measure the change in cell impedance for cells that are treated with a series concentration of CBD for 24 h. AlamarBlue and annexin V/7-AAD staining assays show that CBD has a cytotoxic effect on cell viability and induces cell apoptosis. ECIS analysis shows that CBD decreases the overall resistance and morphological parameters at 4 kHz in a concentration-dependent manner. There is a significant reduction in the wound-healing recovery rate for cells that are treated with 30 μM CBD. This study demonstrates that ECIS can be used for in vitro screening of new chemotherapy and is more sensitive, functional, and comprehensive than traditional biochemical assays. CBD also increases cytotoxicity on cell survival and the migration of oral cancer cells, so it may be a therapeutic drug for oral cancer. Full article
(This article belongs to the Special Issue Oral Fibrosis and Oral Cancer: From Molecular Targets to Therapeutics 2.0)
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14 pages, 3570 KiB  
Article
Butylidenephthalide Abrogates the Snail-Induced Cancer Stemness in Oral Carcinomas
by Pei-Yin Chen, Shih-Chi Chao, Pei-Ling Hsieh, Yi-Wen Liao, Pei-Ming Chu, Horng-Jyh Harn and Cheng-Chia Yu
Int. J. Mol. Sci. 2022, 23(11), 6157; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23116157 - 31 May 2022
Cited by 5 | Viewed by 1908
Abstract
Oral cancer is one of the most common cancers worldwide, especially in South Central Asia. It has been suggested that cancer stem cells (CSC) play crucial roles in tumor relapse and metastasis, and approaches to target CSC may lead to promising results. Here, [...] Read more.
Oral cancer is one of the most common cancers worldwide, especially in South Central Asia. It has been suggested that cancer stem cells (CSC) play crucial roles in tumor relapse and metastasis, and approaches to target CSC may lead to promising results. Here, aldehyde dehydrogenase 1 (ALDH1) and CD44 were utilized to isolate CSCs of oral cancer. Butylidenephthalide, a bioactive phthalide compound from Angelica sinensis, was tested for its anti-CSC effects. MTT assay showed that a lower concentration of butylidenephthalide was sufficient to inhibit the proliferation of patient-derived ALDH1+/CD44+ cells without affecting normal cells. Administration of butylidenephthalide not only reduced ALDH1 activity and CD44 expression, it also suppressed the migration, invasion, and colony formation abilities of ALDH1+/CD44+ cells using a transwell system and clonogenic assay. A patient-derived xenograft mouse model supported our in vitro findings that butylidenephthalide possessed the capacity to retard tumor development. We found that butylidenephthalide dose-dependently downregulated the gene and protein expression of Sox2 and Snail. Our results demonstrated that overexpression of Snail in ALDH1-/CD44- (non-CSCs) cells induced the CSC phenotypes, whereas butylidenephthalide treatment successfully diminished the enhanced self-renewal and propagating properties. In summary, this study showed that butylidenephthalide may serve as an adjunctive for oral cancer therapy. Full article
(This article belongs to the Special Issue Oral Fibrosis and Oral Cancer: From Molecular Targets to Therapeutics 2.0)
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14 pages, 3141 KiB  
Article
miR-31-NUMB Cascade Modulates Monocarboxylate Transporters to Increase Oncogenicity and Lactate Production of Oral Carcinoma Cells
by Chung-Hsien Chou, Chun-Yu Fan Chiang, Cheng-Chieh Yang, Ying-Chieh Liu, Sih-Rou Chang, Kuo-Wei Chang and Shu-Chun Lin
Int. J. Mol. Sci. 2021, 22(21), 11731; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111731 - 29 Oct 2021
Cited by 6 | Viewed by 1978
Abstract
Oral squamous cell carcinoma (OSCC) is among the leading causes of cancer-associated death worldwide. miR-31 is an oncogenic miRNA in OSCC. NUMB is an adaptor protein capable of suppressing malignant transformation. Disruption of the miR-31-NUMB regulatory axis has been demonstrated in [...] Read more.
Oral squamous cell carcinoma (OSCC) is among the leading causes of cancer-associated death worldwide. miR-31 is an oncogenic miRNA in OSCC. NUMB is an adaptor protein capable of suppressing malignant transformation. Disruption of the miR-31-NUMB regulatory axis has been demonstrated in malignancies. Mitochondrial dysfunction and adaptation to glycolytic respiration are frequent events in malignancies. Monocarboxylate transporters (MCTs) function to facilitate lactate flux in highly glycolytic cells. Upregulation of MCT1 and MCT4 has been shown to be a prognostic factor of OSCC. Here, we reported that miR-31-NUMB can modulate glycolysis in OSCC. Using the CRISPR/Cas9 gene editing strategy, we identified increases in oncogenic phenotypes, MCT1 and MCT4 expression, lactate production, and glycolytic respiration in NUMB-deleted OSCC subclones. Transfection of the Numb1 or Numb4 isoform reversed the oncogenic induction elicited by NUMB deletion. This study also showed, for the first time, that NUMB4 binds MCT1 and MCT4 and that this binding increases their ubiquitination, which may decrease their abundance in cell lysates. The disruptions in oncogenicity and metabolism associated with miR-31 deletion and NUMB deletion were partially rescued by MCT1/MCT4 expression or knockdown. This study demonstrated that NUMB is a novel binding partner of MCT1 and MCT4 and that the miR-31-NUMB-MCT1/MCT4 regulatory cascade is present in oral carcinoma. Full article
(This article belongs to the Special Issue Oral Fibrosis and Oral Cancer: From Molecular Targets to Therapeutics 2.0)
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15 pages, 3646 KiB  
Article
LncRNA MIR31HG Drives Oncogenicity by Inhibiting the Limb-Bud and Heart Development Gene (LBH) during Oral Carcinoma
by Kuo-Wei Chang, Wan-Wen Hung, Chung-Hsien Chou, Hsi-Feng Tu, Shi-Rou Chang, Ying-Chieh Liu, Chung-Ji Liu and Shu-Chun Lin
Int. J. Mol. Sci. 2021, 22(16), 8383; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168383 - 04 Aug 2021
Cited by 9 | Viewed by 1974
Abstract
The miR-31 host gene (MIR31HG) encodes a long non-coding RNA (LncRNA) that harbors miR-31 in its intron 2; miR-31 promotes malignant neoplastic progression. Overexpression of MIR31HG and of miR-31 occurs during oral squamous cell carcinoma (OSCC). However, the downstream effectors modulated [...] Read more.
The miR-31 host gene (MIR31HG) encodes a long non-coding RNA (LncRNA) that harbors miR-31 in its intron 2; miR-31 promotes malignant neoplastic progression. Overexpression of MIR31HG and of miR-31 occurs during oral squamous cell carcinoma (OSCC). However, the downstream effectors modulated by MIR31HG during OSCC pathogenesis remain unclear. The present study identifies up-regulation of MIR31HG expression during the potentially premalignant disorder stage of oral carcinogenesis. The potential of MIR31HG to enhance oncogenicity and to activate Wnt and FAK was identified when there was exogenous MIR31HG expression in OSCC cells. Furthermore, OSCC cell subclones with MIR31HG deleted were established using a Crispr/Cas9 strategy. RNA sequencing data obtained from cells expressing MIR31HG, cells with MIR31HG deleted and cells with miR-31 deleted identified 17 candidate genes that seem to be modulated by MIR31HG in OSCC cells. A TCGA database algorithm pinpointed MMP1, BMP2 and Limb-Bud and Heart development (LBH) as effector genes controlled by MIR31HG during OSCC. Exogenous LBH expression decreases tumor cell invasiveness, while knockdown of LBH reverses the oncogenic suppression present in MIR31HG deletion subclones. The study provides novel insights demonstrating the contribution of the MIR31HG-LBH cascade to oral carcinogenesis. Full article
(This article belongs to the Special Issue Oral Fibrosis and Oral Cancer: From Molecular Targets to Therapeutics 2.0)
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Review

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21 pages, 1616 KiB  
Review
Oral Submucous Fibrosis: Etiological Mechanism, Malignant Transformation, Therapeutic Approaches and Targets
by Xiaofeng Qin, Yujie Ning, Liming Zhou and Youming Zhu
Int. J. Mol. Sci. 2023, 24(5), 4992; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24054992 - 05 Mar 2023
Cited by 17 | Viewed by 3887
Abstract
Oral submucosal fibrosis (OSF) is a chronic, progressive and potentially malignant oral disorder with a high regional incidence and malignant rate. With the development of the disease, the normal oral function and social life of patients are seriously affected. This review mainly introduces [...] Read more.
Oral submucosal fibrosis (OSF) is a chronic, progressive and potentially malignant oral disorder with a high regional incidence and malignant rate. With the development of the disease, the normal oral function and social life of patients are seriously affected. This review mainly introduces the various pathogenic factors and mechanisms of OSF, the mechanism of malignant transformation into oral squamous cell carcinoma (OSCC), and the existing treatment methods and new therapeutic targets and drugs. This paper summarizes the key molecules in the pathogenic and malignant mechanism of OSF, the miRNAs and lncRNAs with abnormal changes, and the natural compounds with therapeutic effects, which provides new molecular targets and further research directions for the prevention and treatment of OSF. Full article
(This article belongs to the Special Issue Oral Fibrosis and Oral Cancer: From Molecular Targets to Therapeutics 2.0)
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15 pages, 739 KiB  
Review
Regulation of Ferroptosis by Non-Coding RNAs in Head and Neck Cancers
by Pei-Ling Hsieh, Shih-Chi Chao, Pei-Ming Chu and Cheng-Chia Yu
Int. J. Mol. Sci. 2022, 23(6), 3142; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063142 - 15 Mar 2022
Cited by 5 | Viewed by 3109
Abstract
Ferroptosis is a newly identified mode of programmed cell death characterized by iron-associated accumulation of lipid peroxides. Emerging research on ferroptosis has suggested its implication in tumorigenesis and stemness of cancer. On the other hand, non-coding RNAs have been shown to play a [...] Read more.
Ferroptosis is a newly identified mode of programmed cell death characterized by iron-associated accumulation of lipid peroxides. Emerging research on ferroptosis has suggested its implication in tumorigenesis and stemness of cancer. On the other hand, non-coding RNAs have been shown to play a pivotal role in the modulation of various genes that affect the progression of cancer cells and ferroptosis. In this review, we summarize recent advances in the theoretical modeling of ferroptosis and its relationship between non-coding RNAs and head and neck cancers. Aside from the significance of ferroptosis-related non-coding RNAs in prognostic relevance, we also review how these non-coding RNAs participate in the regulation of iron, lipid metabolism, and reactive oxygen species accumulation. We aim to provide a thorough grounding in the function of ferroptosis-related non-coding RNAs based on current knowledge in an effort to develop effective therapeutic strategies for head and neck cancers. Full article
(This article belongs to the Special Issue Oral Fibrosis and Oral Cancer: From Molecular Targets to Therapeutics 2.0)
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