Long non-coding RNAs in cancer: multifaceted roles and potential targets for immunotherapy.

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.

Awareness data on cervical cancer among females of rural and urban areas of Haryana, India.

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.

Involvement of DPP3 in modulating oncological features and oxidative stress response in esophageal squamous cell carcinoma.

Resistance to therapy in esophageal squamous cell carcinoma (ESCC) is a critical clinical problem and identification of novel therapeutic targets is highly warranted. Dipeptidyl peptidase III (DPP3) is a zinc-dependent aminopeptidase and functions in the terminal stages of the protein turnover. Several studies have reported overexpression and oncogenic functions of DPP3 in numerous malignancies. The present study aimed to determine the expression pattern and functional role of DPP3 in ESCC. DPP3 expression was assessed in normal and tumor tissues using quantitative real-time (qRT)-PCR and corroborated with ESCC gene expression datasets from Gene Expression Omnibus (GEO) and The cancer genome atlas (TCGA). DPP3 stable knockdown was performed in ESCC cells by shRNA and its effect on cell proliferation, migration, cell cycle, apoptosis, and activation of nuclear factor erythroid 2-related factor 2 (NRF2) pathway was assessed. The results suggested that DPP3 is overexpressed in ESCC and its knockdown leads to reduced proliferation, increased apoptosis, and inhibited migration of ESCC cells. Additionally, DPP3 knockdown leads to down-regulation of the NRF2 pathway proteins, such as NRF2, G6PD, and NQO1 along with increased sensitivity toward oxidative stress-induced cell death and chemotherapy. Conclusively, these results demonstrate critical role of DPP3 in ESCC and DPP3/NRF2 axis may serve as an attractive therapeutic target against chemoresistance in this malignancy.

Genetic Diversity of Autosomal STR Markers in the Brahmin Population of Rajasthan and Haryana: Significance in Population and Forensic Genetics.

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.

Targeting epigenetic deregulations for the management of esophageal carcinoma: recent advances and emerging approaches.

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.

Long non-coding RNAs as critical regulators and novel targets in cervical cancer: current status and future perspectives.

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.

Overview of genetic and epigenetic regulation of human papillomavirus and apoptosis in cervical cancer.

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.

Y-23 mediated genetic data analysis of endogamous Brahmin population of Rajasthan, India.

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.

Molecular Associations and Clinical Significance of RAPs in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is an aggressive gastrointestinal malignancy with a high rate of mortality. Multiple studies have individually recognized members of RAP gene family as critical regulators of tumor progression in several cancers, including hepatocellular carcinoma. These studies suffer numerous limitations including a small sample size and lack of analysis of various clinicopathological and molecular features. In the current study, we utilized authoritative multi-omics databases to determine the association of RAP gene family expression and detailed molecular and clinicopathological features in hepatocellular carcinoma (HCC). All five RAP genes were observed to harbor dysregulated expression in HCC compared to normal liver tissues. RAP2A exhibited strongest ability to differentiate tumors from the normal tissues. RAP2A expression was associated with progressive tumor grade, TP53 and CTNNB1 mutation status. Additionally, RAP2A expression was associated with the alteration of its copy numbers and DNA methylation. RAP2A also emerged as an independent marker for patient prognosis. Further, pathway analysis revealed that RAP2A expression is correlated with tumor-infiltrating immune cell composition and oncogenic molecular pathways, such as cell cycle and cellular metabolism.

A Study on Knowledge and Awareness of Cervical Cancer Among Females of Rural and Urban Areas of Haryana, North India.

Lack of awareness of screening methods, risk factors, and symptoms may lead to late diagnosis and poor prognosis of cervical cancer. The plan of this study was to assess the level of awareness about cervical cancer and HPV vaccine among females of rural and urban areas of Haryana, India. This cross-sectional study was performed using a comprehensive self-designed questionnaire on 1500 women of urban (700) and rural (800) background aged 18-65 years, evaluating their knowledge for cervical cancer and screening, HPV infection and its preventive measure, and symptoms and risk factors. Data obtained was analyzed and interpreted by using simple percentages and bar charts. Most of the participants were aged between 21 and 30 years and had college level education. Majority of the women from rural areas had poor knowledge about cervical cancer (55%) and its screening (75%), HPV infection (87.5%), and HPV vaccine (95%) compared with urban areas. Knowledge about symptoms and risk factors was very low in both rural and urban areas. Whatever little knowledge the women had about cervical cancer was from college education, friends, neighbors, relatives, and medical practitioner or doctors. The survey pointed to the critical need to educate women about cervical cancer and its early diagnosis, related risk factors, symptoms, and preventive measures which can be achieved by launching extensive awareness programs for educating females about cervical cancer in India.

High-risk HPV infection modulates the promoter hypermethylation of APC, SFRP1, and PTEN in cervical cancer patients of North India.

Persistent infection with oncogenic HPV and downregulation of tumor suppressor genes play an essential role in the development and progression of cervical cancer. The present study aimed to identify the promoter methylation status of APC, SFRP1, and PTEN which are important regulators of Wnt pathway and their association with high-risk HPV infection and gene expression. Methylation Specific PCR (MSP) and quantitative reverse transcription PCR (RT-qPCR) were used to detect methylation status and gene expression levels of APC, SFRP1, and PTEN in cervical cancer biopsies (110) and paired non-cancerous biopsies (28). APC promoter was methylated in 38%, SFRP1 in 95%, and PTEN in 55% of the cervical cancer biopsies. Our data showed a trend of a higher rate of methylation of the gene promoters in cervical cancer biopsies while; they were majorly un-methylated in non-cancerous biopsies. Corresponding to a higher rate of methylation in cancer biopsies, the gene expression levels of APC, SFRP1, and PTEN were reduced in cervical cancer samples in comparison to normal cervix tissues. Further, we observed that 97% cancer biopsies were HPV infected and high-risk type HPV16 and 18 infections were significantly positively associated with APC (p = 0.008 and p = 0.007), SFRP1 (p = 0.003 and p = 0.0067), and PTEN (p = 0.049 and p = 0.008) promoter methylation. APC, SFRP1, and PTEN promoter hyper-methylation is positively associated with high-risk HPV infection and inversely associated with gene expression. Our findings show that high-risk HPV infection promotes methylation of these genes and further promotes their silencing.

Aberrant promoter methylation of NOTCH1 and NOTCH3 and its association with cervical cancer risk factors in North Indian population.

Cervical cancer is the fourth most common type of cancer in women worldwide, and associated mortality is highest in developing countries like India. Limited studies are available on the role of NOTCH signaling pathway and promoter methylation in cervical cancer. In the current study, we investigated the promoter methylation status of NOTCH receptor genes (mainly NOTCH1, NOTCH2, and NOTCH3) and its correlation with gene expression, clinicopathological factors, and prognosis of cervical cancer. A total cohort of 110 cervical cancer patients of North Indian origin was enrolled in the study. From 28 of these patients, biopsies from adjacent non-cancerous tissue were available to serve as healthy controls. Promoter methylation status and mRNA expression level of NOTCH1, NOTCH2, and NOTCH3 were determined by methylation-specific PCR (MSP) and real-time quantitative (RT-qPCR), respectively. NOTCH1 and NOTCH3 promoters were methylated in 92% (P<0.0001), and 61% (P<0.001) of the cervical cancer biopsies. We did not observe a statistically significant change in the promoter methylation level of NOTCH2. Further, NOTCH1, NOTCH2, and NOTCH3 were down-regulated in cervical cancer biopsies, but the differential expression of only NOTCH1 was found statistically significant. The promoter methylation levels of all three genes also showed a statistically significant association with clinicopathological factors and HPV infection (Type 16 and 18) but we did not observe a statistically significant relationship between their methylation status and gene expression. Overall our results provide evidence of the altered methylation and expression status of NOTCH1 and NOTCH3 receptor genes in cervical cancer. This study of NOTCH gene promoter methylation may provide a new perspective for early screening and diagnosis of cervical cancer.