RESUMO
Cancer remains a major global health concern with high mortality rates mainly due to late diagnosis and poor prognosis. Long non-coding RNAs (lncRNAs) are emerging as key regulators of gene expression in human cancer, functioning through various mechanisms including as competing endogenous RNAs (ceRNAs) and indirectly regulating miRNA expression. LncRNAs have been found to have both oncogenic and tumor-suppressive roles in cancer, with the former promoting cancer cell proliferation, migration, invasion, and poor prognosis. Recent research has shown that lncRNAs are expressed in various immune cells and are involved in cancer cell immune escape and the modulation of the tumor microenvironment, thus highlighting their potential as targets for cancer immunotherapy. Targeting lncRNAs in cancer or immune cells could enhance the anti-tumor immune response and improve cancer immunotherapy outcomes. However, further research is required to fully understand the functional roles of lncRNAs in cancer and the immune system and their potential as targets for cancer immunotherapy. This review offers a comprehensive examination of the multifaceted roles of lncRNAs in human cancers, with a focus on their potential as targets for cancer immunotherapy. By exploring the intricate mechanisms underlying lncRNA-mediated regulation of cancer cell proliferation, invasion, and immune evasion, we provide insights into the diverse therapeutic applications of these molecules.
Assuntos
Imunoterapia , Neoplasias , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/imunologia , Neoplasias/terapia , Neoplasias/genética , Neoplasias/imunologia , Imunoterapia/métodos , Microambiente Tumoral/imunologia , Regulação Neoplásica da Expressão Gênica , Animais , Proliferação de CélulasRESUMO
Three-stranded DNA: RNA hybrids known as R-loops form when the non-template DNA strand is displaced and the mRNA transcript anneals to its template strand. Although R-loop formation controls DNA damage response, mitochondrial and genomic transcription, and physiological R-loop formation, imbalanced formation of R-loop can jeopardize a cell's genomic integrity. Transcription regulation and immunoglobulin class switch recombination are two further specialized functions of genomic R-loops. R-loop formation has a dual role in the development of cancer and disturbed R-loop homeostasis as observed in several malignancies. R-loops transcribe at the telomeric and pericentromeric regions, develop in the space between long non-coding RNAs and telomeric repeats, and shield telomeres. In bacteria and archaea, R-loop development is a natural defence mechanism against viruses which also causes DNA degradation. Their emergence in the mammalian genome is controlled, suggesting that they were formed as an inevitable byproduct of RNA transcription but also co-opted for regulatory functions. R-loops may be engaged in cell physiology by regulating gene expression. R-loop biology is probably going to remain a fascinating field of study for a very long time as it offers many avenues for R-loop research.
Assuntos
Estruturas R-Loop , Estruturas R-Loop/genética , Humanos , Animais , Genoma/genética , Transcrição Gênica , DNA/genética , DNA/metabolismo , Telômero/genética , Telômero/metabolismo , RNA/genética , RNA/metabolismo , Regulação da Expressão Gênica/genética , RNA Longo não Codificante/genéticaRESUMO
Human papillomavirus (HPV), a common cause of sexually transmitted diseases, may cause warts and lead to various types of cancers, which makes it important to understand the risk factors associated with it. HPV is the leading risk factor and plays a crucial role in the progression of cervical cancer. Viral oncoproteins E6 and E7 play a pivotal role in this process. Beyond cervical cancer, HPV-associated cancers of the mouth and throat are also increasing. HPV can also contribute to other malignancies like penile, vulvar, and vaginal cancers. Emerging evidence links HPV to these cancers. Research on the oncogenic effect of HPV is still ongoing and explorations of screening techniques, vaccination, immunotherapy and targeted therapeutics are all in progress. The present review offers valuable insight into the current understanding of the role of HPV in cancer and its potential implications for treatment and prevention in the future.
Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/complicações , Feminino , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/etiologia , Papillomaviridae/patogenicidade , Neoplasias/virologia , Neoplasias/terapia , Proteínas Oncogênicas Virais/metabolismo , Proteínas Oncogênicas Virais/genética , Fatores de Risco , MasculinoRESUMO
Cervical cancer is the fourth most common cancer affecting women worldwide after breast, colorectal and lung cancers. Owing to a lack of awareness and resources, low- and middle-income countries bear most of the burden of cervical cancer. In developed countries, the incidence rate has been halved over the past three decades due to robust screening and implementation of vaccine programs. HPV is not the sole cause of cervical cancer but acts as a principal factor in the pathogenesis of cervical cancer. By integrating into the host genome, its oncogenic proteins (E6 and E7) alter and interfere with the standard signal transduction machinery of the host. Apoptosis is a key pathway affected by aberrant genetic mutations, polymorphisms and epigenetic mechanisms during cervical carcinogenesis. Along with DNA methylation and histone modifications, non-coding RNAs have also been implicated as epigenetic modulators in various malignancies and are being explored for reversing disease severity. This review emphasizes various genetic and epigenetic approaches regulating apoptotic pathways and HPV E6 and E7 genes that can be targeted to overcome the challenges in cervical cancer treatment. In addition, it also discusses the apoptosis targeting novel drug molecules in cervical cancer which are currently undergoing clinical and pre-clinical trials.
Assuntos
Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Papillomavirus Humano , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/diagnóstico , Epigênese Genética , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/metabolismo , Apoptose/genética , Proteínas Oncogênicas Virais/genéticaRESUMO
Cervical cancer is among the leading causes of cancer-associated mortality in women. In spite of vaccine availability, improved screening procedures, and chemoradiation therapy, cervical cancer remains the most commonly diagnosed cancer in 23 countries and the leading cause of cancer deaths in 36 countries. There is, therefore, a need to come up with novel diagnostic and therapeutic targets. Long non-coding RNAs (lncRNAs) play a remarkable role in genome regulation and contribute significantly to several developmental and disease pathways. The deregulation of lncRNAs is often observed in cancer patients, where they are shown to affect multiple cellular processes, including cell cycle, apoptosis, angiogenesis, and invasion. Many lncRNAs are found to be involved in the pathogenesis as well as progression of cervical cancer and have shown potency to track metastatic events. This review provides an overview of lncRNA mediated regulation of cervical carcinogenesis and highlights their potential as diagnostic and prognostic biomarkers as well as therapeutic targets for cervical cancer. In addition, it also discusses the challenges associated with the clinical implication of lncRNAs in cervical cancer.
Assuntos
RNA Longo não Codificante , Neoplasias do Colo do Útero , Humanos , Feminino , RNA Longo não Codificante/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Apoptose/genética , Carcinogênese/genéticaRESUMO
Ranking from seventh in incidence to sixth in mortality, esophageal carcinoma is considered a severe malignancy of food pipe. Later-stage diagnosis, drug resistance, and a high mortality rate contribute to its lethality. Esophageal squamous cell carcinoma and esophageal adenocarcinoma are the two main histological subtypes of esophageal carcinoma, with squamous cell carcinoma alone accounting for more than eighty percent of its cases. While genetic anomalies are well known in esophageal cancer, accountability of epigenetic deregulations is also being explored for the recent two decades. DNA methylation, histone modifications, and functional non-coding RNAs are the crucial epigenetic players involved in the modulation of different malignancies, including esophageal carcinoma. Targeting these epigenetic aberrations will provide new insights into the development of biomarker tools for risk stratification, early diagnosis, and effective therapeutic intervention. This review discusses different epigenetic alterations, emphasizing the most significant developments in esophageal cancer epigenetics and their potential implication for the detection, prognosis, and treatment of esophageal carcinoma. Further, the preclinical and clinical status of various epigenetic drugs has also been reviewed.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Epigênese Genética/genética , Metilação de DNA/genéticaRESUMO
HOX genes constitute a family of evolutionarily conserved transcription factors that play pivotal roles in embryonic development, tissue patterning, and cell differentiation. These genes are essential for the precise spatial and temporal control of body axis formation in vertebrates. In addition to their developmental functions, HOX genes have garnered significant attention for their involvement in various diseases, including cancer. Deregulation of HOX gene expression has been observed in numerous malignancies, where they can influence tumorigenesis, progression, and therapeutic responses. This review provides an overview of the diverse roles of HOX genes in development, disease, and potential therapeutic targets, highlighting their significance in understanding biological processes and their potential clinical implications.
Assuntos
Genes Homeobox , Neoplasias , Humanos , Neoplasias/genética , Neoplasias/terapia , Neoplasias/patologia , Animais , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Carcinogênese/genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismoRESUMO
A cross-sectional study was done to assess the degree of current awareness and behaviors about cervical cancer among females in urban and rural areas of North India. This survey was conducted on one thousand females (500 rural and 500 urban). A well-structured questionnaire was designed to collect information about participants' knowledge on cancer of cervix uteri such as age, height and weight measurements, marital status, menstrual status, personal hygiene, age at menarche, sexual history, pregnancy and abortion history, use of contraceptive pills for birth-control, smoking, alcohol consumption, and other relevant information. The data was collected by conducting face-to-face interviews after obtaining the verbal consent of the participants. The data has the potential to reduce disease burden by spreading awareness about symptoms and risk factors of cervical cancer as well as implementation of effective early screening strategies.
RESUMO
The aim of the study is to evaluate the suitability of STRs for molecular characterization and forensic applications in unrelated Brahmins of Rajasthan and Haryana states, India. Materials and Methods: A total of 203 male DNA samples from various districts of Haryana (n=104) and Rajasthan (n=99) were genotyped using the GlobalFiler® PCR Amplification Kit. Allelic frequencies and different forensic parameters like PD, PE, PIC, PM, Ho, He, UHe, and TPI were calculated with different software. Results: More than 200 alleles were present in both populations, ranging from 6.0 to 35.2 and SE33 was the most polymorphic marker. The combined power of discrimination was 1. To know the relatedness with other Indian Brahmin populations, the UPGMA dendrogram and principal component analysis plot were visualized to show that both populations are close to each other and in nearby Saraswat Brahmins of Himachal Pradesh. This study showed a genetic relationship and forensic examination in the Haryana and Rajasthan Brahmin populations and various ethno-linguistically diverse populations of India. Conclusion: The results imply that the highly polymorphic 21 autosomal STR loci might be applied for individuals' forensic identification and parentage testing. This study also suggests that the kit having both autosomal and Y-STR markers is appropriate for a better understanding of the genetic and forensic examination in the Brahmin population of Haryana and Rajasthan.
Assuntos
Povo Asiático , Genética Forense , Humanos , Masculino , Índia , Alelos , Variação Genética/genéticaRESUMO
India's largest state Rajasthan is known for its variable population groups including castes, communities and tribes. In the present article, Y-STR polymorphisms of hundred unrelated healthy male volunteers from the Brahmin population of Rajasthan, India were investigated using the Powerplex® Y-23 PCR amplification kit. Total 94 distinct haplotypes were obtained out of them 93 were singletons. Haplotype Diversity (HD) and Discrimination Capacity (DC) for the population were 0.644 and 0.9894 respectively. The Intra-population relationship between the present population data and other reported Indian populations was examined through Multidimensional Scaling (MDS) Plot, which shows the Brahmin population of Rajasthan lies in a cluster with the Brahmin populations of Haryana and Maharashtra. Data generated with 23 Y-STR markers is submitted on Y chromosome haplotype reference database (YHRD) (yhrd.org) and it will robust the forensic database of the Rajasthan population of India.