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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 (30 April 2023) | Viewed by 25427

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Special Issue Editor

Prof. Dr. Bonglee Kim

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Guest Editor

Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
Interests: oncology; epigenetics; miRNA; natural products; cancer; antioxidants; apoptosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

MicroRNAs (miRNAs) are small noncoding RNAs about 18–24 nucleotides in length that have roles in cellular homeostasis functions in proliferation, cell cycle, development, differentiation, growth, and apoptosis. Various human diseases including multiple sclerosis, diabetes, nonalcoholic fatty liver disease, and cancer have been associated with deregulated miRNA expression. The aberrant expression of miRNAs is shown in various cancers. Recently, miRNAs have been identified as potential biomarkers for cancer diagnosis and response to therapy. However, the full mechanism of miRNA in cancer therapy is not still unknown. Several drugs including natural products have reported to have miRNA regulatory effect in cancer pathology including apoptosis, autophagy, drug resistance, invasion, metastasis, angiogenesis, etc.

In this Special Issue entitled “MicroRNAs in Cancer Therapy”, recent advances in miRNA studies in cancer therapy, including are of interest.

Prof. Dr. Bonglee Kim
Guest Editor

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Keywords

miRNA
cancer
apoptosis
proliferation
metastasis
resistance
chemotherapy
natural product
herbal medicine
plant extract
side effects of chemotherapy

Published Papers (10 papers)

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Research

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14 pages, 3218 KiB

Open AccessArticle

miR-145 as a Potential Biomarker and Therapeutic Target in Patients with Non-Small Cell Lung Cancer

by William C. Cho, Chi F. Wong, Kwan P. Li, Alvin H. Fong, King Y. Fung and Joseph S. Au

Int. J. Mol. Sci. 2023, 24(12), 10022; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241210022 - 12 Jun 2023

Cited by 2 | Viewed by 1376

Abstract

Our previous study found that miR-145 was downregulated in non-small cell lung cancer (NSCLC) tissues and that it could inhibit the cell proliferation in transfected NSCLC cells. In this study, we found that miR-145 was downregulated in NSCLC plasma samples compared to healthy controls. A receiver operating characteristic curve analysis indicated that plasma miR-145 expression was correlated with NSCLC in patient samples. We further revealed that the transfection of miR-145 inhibited the proliferation, migration, and invasion of NSCLC cells. Most importantly, miR-145 significantly delayed the tumor growth in a mouse model of NSCLC. We further identified GOLM1 and RTKN as the direct targets of miR-145. A cohort of paired tumors and adjacent non-malignant lung tissues from NSCLC patients was used to confirm the downregulated expression and diagnostic value of miR-145. The results were highly consistent between our plasma and tissue cohorts, confirming the clinical value of miR-145 in different sample groups. In addition, we also validated the expressions of miR-145, GOLM1, and RTKN using the TCGA database. Our findings suggested that miR-145 is a regulator of NSCLC and it plays an important role in NSCLC progression. This microRNA and its gene targets may serve as potential biomarkers and novel molecular therapeutic targets in NSCLC patients. Full article

(This article belongs to the Special Issue MicroRNAs in Cancer Therapy)

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11 pages, 1110 KiB

Open AccessArticle

A Tumor and Immune-Related Micro-RNA Signature Predicts Relapse-Free Survival of Melanoma Patients Treated with Ipilimumab

by Iyad Kobeissi, Islam Eljilany, Tala Achkar, William A. LaFramboise, Lucas Santana-Santos and Ahmad A. Tarhini

Int. J. Mol. Sci. 2023, 24(9), 8167; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24098167 - 03 May 2023

Cited by 2 | Viewed by 1618

Abstract

Despite the unprecedented advances in the treatment of melanoma with immunotherapy, there continues to be a major need for biomarkers of clinical benefits and immune resistance associated with immune checkpoint inhibitors; microRNA could play a vital role in these efforts. This study planned to identify differentially expressed miRNA molecules that may have prognostic value for clinical benefits. Patients with surgically operable regionally advanced melanoma were treated with neoadjuvant ipilimumab (10 mg/kg intravenously every 3 weeks × two doses) bracketing surgery. Tumor biospecimens were obtained at baseline and surgery, and microRNA (miRNA) expression profiling was performed on the tumor biopsies. We found that an expression profile consisting of a 4-miRNA signature was significantly associated with improved relapse-free survival (RFS). The signature consisted of biologically relevant molecules previously reported to have prognostic value in melanoma and other malignancies, including miR-34c, miR-711, miR-641, and miR-22. Functional annotation analysis of target genes for the 4-miRNA signature was significantly enriched for various cancer-related pathways, including cell proliferation regulation, apoptosis, the MAPK signaling pathway, and the positive regulation of T cell activation. Our results presented miRNAs as potential biomarkers that can guide the treatment of melanoma with immune checkpoint inhibitors. These findings warrant further investigation in relation to CTLA4 blockade and other immune checkpoint inhibitors. ClinicalTrials.gov NCT00972933. Full article

(This article belongs to the Special Issue MicroRNAs in Cancer Therapy)

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20 pages, 2733 KiB

Open AccessArticle

Novel MicroRNA-Regulated Transcript Networks Are Associated with Chemotherapy Response in Ovarian Cancer

by Danai G. Topouza, Jihoon Choi, Sean Nesdoly, Anastasiya Tarnouskaya, Christopher J. B. Nicol and Qing Ling Duan

Int. J. Mol. Sci. 2022, 23(9), 4875; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23094875 - 28 Apr 2022

Cited by 1 | Viewed by 2253

Abstract

High-grade serous ovarian cancer (HGSOC) is a highly lethal gynecologic cancer, in part due to resistance to platinum-based chemotherapy reported among 20% of patients. This study aims to generate novel hypotheses of the biological mechanisms underlying chemotherapy resistance, which remain poorly understood. Differential expression analyses of mRNA- and microRNA-sequencing data from HGSOC patients of The Cancer Genome Atlas identified 21 microRNAs associated with angiogenesis and 196 mRNAs enriched for adaptive immunity and translation. Coexpression network analysis identified three microRNA networks associated with chemotherapy response enriched for lipoprotein transport and oncogenic pathways, as well as two mRNA networks enriched for ubiquitination and lipid metabolism. These network modules were replicated in two independent ovarian cancer cohorts. Moreover, integrative analyses of the mRNA/microRNA sequencing and single-nucleotide polymorphisms (SNPs) revealed potential regulation of significant mRNA transcripts by microRNAs and SNPs (expression quantitative trait loci). Thus, we report novel transcriptional networks and biological pathways associated with resistance to platinum-based chemotherapy in HGSOC patients. These results expand our understanding of the effector networks and regulators of chemotherapy response, which will help to improve the management of ovarian cancer. Full article

(This article belongs to the Special Issue MicroRNAs in Cancer Therapy)

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13 pages, 3099 KiB

Open AccessArticle

Targeting of Mcl-1 Expression by MiRNA-3614-5p Promotes Cell Apoptosis of Human Prostate Cancer Cells

by Yi-Hsien Hsieh, Fang-Jung Yu, Yasser Nassef, Chung-Jung Liu, Yong-Syuan Chen, Ching-Yi Lin, Jia-Liang Feng and Min-Hua Wu

Int. J. Mol. Sci. 2022, 23(8), 4194; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23084194 - 11 Apr 2022

Cited by 6 | Viewed by 1848

Abstract

MicroRNA (miRNA) acts as a critical regulator of growth in various human malignancies. However, the role of miRNA-3614 in the progression of human prostate cancer remains unknown. In this study, our results demonstrated that miRNA-3614-5p exerts a significant inhibitory effect on cell viability and colony formation and induces sub-G1 cell cycle arrest and apoptosis in human prostate cancer cells. Myeloid cell leukemia-1 (Mcl-1) acts as a master regulator of cell survival. Using the miRNA databases, miRNA-3614-5p was found to regulate Mcl-1 expression by targeting positions of the Mcl-1-3′ UTR. The reduction of Mcl-1 expression by miRNA-3614-5p was further confirmed using an immunoblotting assay. Pro-apoptotic caspase-3 and poly (ADP-ribose) polymerase (PARP) were significantly activated by miRNA-3614-5p to generate cleaved caspase-3 (active caspase-3) and cleaved PARP (active PARP), accompanied by the inhibited Mcl-1 expression. These findings were the first to demonstrate the anti-growth effects of miRNA-3614-5p through downregulating Mcl-1 expression in human prostate cancer cells. Full article

(This article belongs to the Special Issue MicroRNAs in Cancer Therapy)

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17 pages, 2302 KiB

Open AccessArticle

Impact of Oncogenic Targets by Tumor-Suppressive miR-139-5p and miR-139-3p Regulation in Head and Neck Squamous Cell Carcinoma

by Ayaka Koma, Shunichi Asai, Chikashi Minemura, Sachi Oshima, Takashi Kinoshita, Naoko Kikkawa, Keiichi Koshizuka, Shogo Moriya, Atsushi Kasamatsu, Toyoyuki Hanazawa, Katsuhiro Uzawa and Naohiko Seki

Int. J. Mol. Sci. 2021, 22(18), 9947; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22189947 - 14 Sep 2021

Cited by 9 | Viewed by 2182

Abstract

We newly generated an RNA-sequencing-based microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC). Analysis of the signature revealed that both strands of some miRNAs, including miR-139-5p (the guide strand) and miR-139-3p (the passenger strand) of miR-139, were downregulated in HNSCC tissues. Analysis of The Cancer Genome Atlas confirmed the low expression levels of miR-139 in HNSCC. Ectopic expression of these miRNAs attenuated the characteristics of cancer cell aggressiveness (e.g., cell proliferation, migration, and invasion). Our in silico analyses revealed a total of 28 putative targets regulated by pre-miR-139 (miR-139-5p and miR-139-3p) in HNSCC cells. Of these, the GNA12 (guanine nucleotide-binding protein subunit alpha-12) and OLR1 (oxidized low-density lipoprotein receptor 1) expression levels were identified as independent factors that predicted patient survival according to multivariate Cox regression analyses (p = 0.0018 and p = 0.0104, respectively). Direct regulation of GNA12 and OLR1 by miR-139-3p in HNSCC cells was confirmed through luciferase reporter assays. Moreover, overexpression of GNA12 and OLR1 was detected in clinical specimens of HNSCC through immunostaining. The involvement of miR-139-3p (the passenger strand) in the oncogenesis of HNSCC is a new concept in cancer biology. Our miRNA-based strategy will increase knowledge on the molecular pathogenesis of HNSCC. Full article

(This article belongs to the Special Issue MicroRNAs in Cancer Therapy)

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Review

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24 pages, 1199 KiB

Open AccessReview

The Roles of MiRNAs (MicroRNAs) in Melanoma Immunotherapy

by Linyinxue Dong, Xuechen Tian, Yunqi Zhao, Haohong Tu, Aloysius Wong and Yixin Yang

Int. J. Mol. Sci. 2022, 23(23), 14775; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232314775 - 25 Nov 2022

Cited by 4 | Viewed by 2172

Abstract

Melanoma is the most aggressive form of skin cancer, characterized by life-threatening and rapidly spreading progression. Traditional targeted therapy can alleviate tumors by inactivating hyperactive kinases such as BRAF or MEK but inevitably encounters drug resistance. The advent of immunotherapy has revolutionized melanoma treatment and significantly improved the prognosis of melanoma patients. MicroRNAs (miRNAs) are intricately involved in innate and adaptive immunity and are implicated in melanoma immunotherapy. This systematic review describes the roles of miRNAs in regulating the functions of immune cells in skin and melanoma, as well as the involvement of miRNAs in pharmacology including the effect, resistance and immune-related adverse events of checkpoint inhibitors such as PD-1 and CTLA-4 inhibitors, which are used for treating cutaneous, uveal and mucosal melanoma. The expressions and functions of miRNAs in immunotherapy employing tumor-infiltrating lymphocytes and Toll-like receptor 9 agonists are also discussed. The prospect of innovative therapeutic strategies such as the combined administration of miRNAs and immune checkpoint inhibitors and the nanotechnology-based delivery of miRNAs are also provided. A comprehensive understanding of the interplay between miRNAs and immunotherapy is crucial for the discovery of reliable biomarkers and for the development of novel miRNA-based therapeutics against melanoma. Full article

(This article belongs to the Special Issue MicroRNAs in Cancer Therapy)

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29 pages, 2182 KiB

Open AccessReview

miRNA: A Promising Therapeutic Target in Cancer

by Amrutha Menon, Noraini Abd-Aziz, Kanwal Khalid, Chit Laa Poh and Rakesh Naidu

Int. J. Mol. Sci. 2022, 23(19), 11502; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231911502 - 29 Sep 2022

Cited by 68 | Viewed by 4732

Abstract

microRNAs are small non-coding RNAs that regulate several genes post-transcriptionally by complementarity pairing. Since discovery, they have been reported to be involved in a variety of biological functions and pathologies including cancer. In cancer, they can act as a tumor suppressor or oncomiR depending on the cell type. Studies have shown that miRNA-based therapy, either by inhibiting an oncomiR or by inducing a tumor suppressor, is effective in cancer treatment. This review focusses on the role of miRNA in cancer, therapeutic approaches with miRNAs and how they can be effectively delivered into a system. We have also summarized the patents and clinical trials in progress for miRNA therapy. Full article

(This article belongs to the Special Issue MicroRNAs in Cancer Therapy)

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20 pages, 1101 KiB

Open AccessReview

miR-199a: A Tumor Suppressor with Noncoding RNA Network and Therapeutic Candidate in Lung Cancer

by Wei Meng, Yanli Li, Binshu Chai, Xiaomin Liu and Zhongliang Ma

Int. J. Mol. Sci. 2022, 23(15), 8518; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158518 - 31 Jul 2022

Cited by 11 | Viewed by 2724

Abstract

Lung cancer is the leading cause of cancer death worldwide. miR-199a, which has two mature molecules: miR-199a-3p and miR-199a-5p, plays an important biological role in the genesis and development of tumors. We collected recent research results on lung cancer and miR-199a from Google Scholar and PubMed databases. The biological functions of miR-199a in lung cancer are reviewed in detail, and its potential roles in lung cancer diagnosis and treatment are discussed. With miR-199a as the core point and a divergence outward, the interplay between miR-199a and other ncRNAs is reviewed, and a regulatory network covering various cancers is depicted, which can help us to better understand the mechanism of cancer occurrence and provide a means for developing novel therapeutic strategies. In addition, the current methods of diagnosis and treatment of lung cancer are reviewed. Finally, a conclusion was drawn: miR-199a inhibits the development of lung cancer, especially by inhibiting the proliferation, infiltration, and migration of lung cancer cells, inhibiting tumor angiogenesis, increasing the apoptosis of lung cancer cells, and affecting the drug resistance of lung cancer cells. This review aims to provide new insights into lung cancer therapy and prevention. Full article

(This article belongs to the Special Issue MicroRNAs in Cancer Therapy)

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21 pages, 3344 KiB

Open AccessReview

Exosomal and Non-Exosomal MicroRNAs: New Kids on the Block for Cancer Therapy

by Shahzad Nawaz Syed and Bernhard Brüne

Int. J. Mol. Sci. 2022, 23(9), 4493; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23094493 - 19 Apr 2022

Cited by 9 | Viewed by 2729

Abstract

MicroRNAs have been projected as promising tools for diagnostic and prognostic purposes in cancer. More recently, they have been highlighted as RNA therapeutic targets for cancer therapy. Though miRs perform a generic function of post-transcriptional gene regulation, their utility in RNA therapeutics mostly relies on their biochemical nature and their assembly with other macromolecules. Release of extracellular miRs is broadly categorized into two different compositions, namely exosomal (extracellular vesicles) and non-exosomal. This nature of miRs not only affects the uptake into target cells but also poses a challenge and opportunity for RNA therapeutics in cancer. By virtue of their ability to act as mediators of intercellular communication in the tumor microenvironment, extracellular miRs perform both, depending upon the target cell and target landscape, pro- and anti-tumor functions. Tumor-derived miRs mostly perform pro-tumor functions, whereas host cell- or stroma-derived miRs are involved in anti-tumor activities. This review deals with the recent understanding of exosomal and non-exosomal miRs in the tumor microenvironment, as a tool for pro- and anti-tumor activity and prospective exploit options for cancer therapy. Full article

(This article belongs to the Special Issue MicroRNAs in Cancer Therapy)

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17 pages, 1265 KiB

Open AccessReview

The Biological Function of MicroRNAs in Bone Tumors

by Sarah Adriana Scuderi, Giovanna Calabrese, Irene Paterniti, Michela Campolo, Marika Lanza, Anna Paola Capra, Luca Pantaleo, Stefania Munaò, Lorenzo Colarossi, Stefano Forte, Salvatore Cuzzocrea and Emanuela Esposito

Int. J. Mol. Sci. 2022, 23(4), 2348; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23042348 - 21 Feb 2022

Cited by 3 | Viewed by 2518

Abstract

Micro ribonucleic acids (miRNAs) are small endogenous noncoding RNAs molecules that regulate gene expression post-transcriptionally. A single miRNA is able to target hundreds of specific messenger RNA (mRNAs) by binding to the 3′-untranslated regions. miRNAs regulate different biological processes such as cell proliferation, differentiation and apoptosis. Altered miRNA expression is certainly related to the development of the most common human diseases, including tumors. Osteosarcoma (OS), Ewing’s Sarcoma (ES), and Chondrosarcoma (CS) are the most common primary bone tumors which affect mainly children and adolescents. A significant dysregulation of miRNA expression, in particular of mir-34, mir-21, mir-106, mir-143, and miR-100, has been revealed in OS, ES and CS. In this context, miRNAs can act as either tumor suppressor genes or oncogenes, contributing to the initiation and progression of bone tumors. The in-depth study of these small molecules can thus help to better understand their biological functions in bone tumors. Therefore, this review aims to examine the potential role of miRNAs in bone tumors, especially OS, ES and CS, and to suggest their possible use as potential therapeutic targets for the treatment of bone tumors and as biomarkers for early diagnosis. Full article

(This article belongs to the Special Issue MicroRNAs in Cancer Therapy)

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