Vivek Uttam

Despite advances in breast cancer treatment, the number of lives lost each year remains high. One of the significant challenges in treating breast cancer is the highly complex and dynamic tumor microenvironment (TME), which often makes tumors resistant to various kinds of therapies. To overcome this, researchers are tuning and tweaking the body's immune cells, especially T cells and subsets, to clear cancerous cell residues more effectively from the patient's body. Recent research shows that long non-coding RNAs (lncRNAs), once considered "junk" DNA, play an essential role in shaping T cells' plasticity in healthy and cancerous tissues. In this review, we presented and discussed our perspectives on how specific lncRNAs control T-cell infiltration into tumors and how they contribute to immune escape. For example, LINC00472, MIAT, HITT, NKILA, and MALAT1 influence how T cells enter tumors, while SNHG1, TINCR, and GATA3-AS1 help cancer cells hide from immune attack. These lncRNAs can shift the balance between regulatory T cells (Tregs) and cytotoxic T cells (CTLs), either slowing tumor growth or helping cancer evade destruction by recruiting Tregs, M2 macrophages, and myeloid-derived suppressor cells (MDSCs). LncRNAs regulate key signalling pathways such as NF-κB, Wnt/β-catenin, PI3K/AKT, and JAK/STAT, often by acting as "sponges" for miRNAs that regulate immune checkpoints like PD-L1. Further, LncRNAs are found to remodel cytokine and chemokine networks, ultimately reshaping the TME. Overexpression of lncRNA, such as TINCR and MIAT, GATA3-AS1, leads to enhanced PD-L1 deubiquitination, thus aiding in tumor immune evasion. Moreover, our in silico analysis suggests that lncRNAs modulate various immune-related signaling pathways in T cells. Together, these insights reveal how lncRNAs could be harnessed to fine-tune T-cell plasticity, paving the way for more personalized immunotherapies and improving outcomes for breast cancer patients.

Pancreatic (PC), colorectal (CRC), hepatocellular (HCC), and gallbladder (GC) cancers together account for nearly 20% of all cancer cases. However, specific biomarkers and therapeutic targets for these cancers are lacking. Diagnosing these cancers early and providing timely, appropriate treatment to improve patient outcomes is crucial. In this context, previous studies, including ours, have highlighted the potential of non-coding RNAs, particularly long non-coding RNAs (lncRNAs), in diagnosing and prognosis of various cancers. This review focuses on the mechanistic role of the recently identified lncRNA LINC00261 in PC, CRC, HCC, and GC. Our comprehensive literature analysis revealed that LINC00261 functions as a tumor suppressor, and its reduced expression is associated with larger tumor size, advanced tumor-node-metastasis (TNM) stages, lymphatic metastasis, and poorer overall survival rates. Additionally, we discovered that LINC00261 acts as a molecular sponge for miRNAs, such as miR-550a-3p, miR-23a-3p, miR-148a, miR-324-3p, and miR-105-5p, regulating critical cancer-related signaling pathways, including PI3K/Akt/mTOR, Protein kinase B, and Mammalian target of rapamycin (mTOR). Further bioinformatic analysis revealed that LINC00261 regulates key cellular processes, such as protein-DNA complex formation, ribonuclease complex activity, histone deacetylase complexes, and nuclear matrix interactions. Overall, we believe that LINC00261 holds significant promise as a future biomarker and, when combined with existing treatment strategies, may enhance cancer patient care and survival.

Despite being the leading cause of death worldwide, cancer still lacks precise biomarkers for effective targeting, limiting efforts to reduce mortality rates. This review explores the role and clinical significance of a newly identified long non-coding RNA, MYOSLID, in cancer progression. MYOSLID has emerged as a critical modulator in cancer progression by influencing key hallmarks such as proliferation, immune evasion, metastasis, and metabolic reprogramming. It promotes tumor cell growth by stabilizing hypoxia-inducible factor 1 and acting as a competing endogenous RNA (ceRNA) to sequester tumor-suppressive microRNAs like miR-29c-3p, thereby enhancing oncogene expression. It facilitates immune evasion by upregulating PD-L1, suppressing T cell activation, and modulating necroptosis pathways involving RIPK1 and RIPK3. Additionally, MYOSLID drives metastasis by regulating epithelial–mesenchymal transition markers such as LAMB3 and Slug while promoting RAB13-mediated cytoskeletal remodeling and enhancing cancer cell invasion. We have obtained the expression of MYOSLID from TCGA and the ENCORI database. The expression of colorectal adenocarcinoma (COAD) and head and neck squamous cell carcinoma (HNSCC) is associated with poor prognosis and lower survival rate. Given its significant potential as a diagnostic biomarker and therapeutic target, further research is required to elucidate its precise molecular mechanisms and therapeutic applications in cancer treatment.

Pancreatic (PC), colorectal (CRC), hepatocellular (HCC), and gallbladder (GC) cancers together account for nearly 20% of all cancer cases. However, specific biomarkers and therapeutic targets for these cancers are lacking. Diagnosing these cancers early and providing timely, appropriate treatment to improve patient outcomes is crucial. In this context, previous studies, including ours, have highlighted the potential of non-coding RNAs, particularly long non-coding RNAs (lncRNAs), in diagnosing and prognosis various cancers. This review focuses on the mechanistic role of the recently identified lncRNA LINC00261 in PC, CRC, HCC, and GC. Our comprehensive literature analysis revealed that LINC00261 functions as a tumor suppressor, and its reduced expression is associated with larger tumor size, advanced tumor-node-metastasis (TNM) stages, lymphatic metastasis, and poorer overall survival rates. Additionally, we discovered that LINC00261 acts as a molecular sponge for miRNAs such as miR-550a-3p, miR-23a-3p, miR-148a, miR-324-3p, and miR-105-5p, regulating critical cancer-related signaling pathways, including PI3K/Akt/mTOR, Protein kinase B, and Mammalian target of rapamycin (mTOR). Further bioinformatic analysis revealed that LINC00261 regulates key cellular processes such as protein-DNA complex formation, ribonuclease complex activity, histone deacetylase complexes, and nuclear matrix interactions. Overall, we believe that LINC00261 holds significant promise as a future biomarker and, when combined with existing treatment strategies, may enhance cancer patient care and survival.

Despite being the leading cause of death worldwide, cancer still lacks precise biomarkers for effective targeting, limiting efforts to reduce mortality rates. This review explores the role and clinical significance of the newly identified long non-coding RNA, MYOSLID, in cancer progression. MYOSLID has emerged as a critical modulator in cancer progression by influencing key hallmarks such as proliferation, immune evasion, metastasis, and metabolic reprogramming. It promotes tumor cell growth by stabilizing hypoxia-inducible factor 1 and acting as a competing endogenous RNA (ceRNA) to sequester tumor-suppressive microRNAs like miR-29c-3p, thereby enhancing oncogene expression. It facilitates immune evasion by upregulating PD-L1, suppressing T-cell activation, and modulating necroptosis pathways involving RIPK1 and RIPK3. Additionally, MYOSLID drives metastasis by regulating epithelial-mesenchymal transition markers such as LAMB3 and Slug while promoting RAB13-mediated cytoskeletal remodeling and enhancing cancer cell invasion. High MYOSLID expression is associated with poor prognosis in cancers such as colorectal adenocarcinoma (COAD) and head and neck squamous cell carcinoma (HNSCC). Given its significant potential as a diagnostic biomarker and therapeutic target, further research is required to elucidate its precise molecular mechanisms and therapeutic applications in cancer treatment.

Despite strides in diagnostic and therapeutic approaches for ESCC, patient survival rates remain relatively low. Recent studies highlight the pivotal role of long non-coding RNAs (lncRNAs) in regulating diverse cellular activities in humans. Dysregulated lncRNAs have emerged as potential diagnostic indicators across various cancers, including ESCC. However, further research is necessary to effectively leverage ESCC-associated lncRNAs in clinical settings. Understanding their clinical significance for ESCC diagnosis and their mechanisms can pave the way for more effective therapeutic strategies. Our qRT-PCR analysis revealed significant downregulation of SOX2-OT (~ 2.02-fold) and NEAT1 (~ 1.53-fold) in ESCC blood samples. These lncRNAs show potential as biomarkers for distinguishing ESCC patients from healthy individuals, with ROC curves and AUC values of 0.736 for SOX2-OT and 0.621 for NEAT1. Further analysis examined the correlation between SOX2-OT and NEAT1 expression and various clinicopathological factors, including age, gender, smoking, alcohol use, hot beverage intake, tumor grade, and TNM stages. In-silico studies highlighted their roles in miRNA sponging via mTOR and MAPK pathways, while co-expression network analysis identified associated genes. This research paves the way for future studies on ESCC prognosis using SOX2-OT and NEAT1 as predictive markers. By thoroughly investigating the functions of these lncRNAs, we aim to deepen our understanding of their potential as diagnostic markers and their role in facilitating effective therapeutic interventions for esophageal squamous cell carcinoma (ESCC) within clinical contexts.

Lung cancer is a severe challenge to the health care system with intrinsic resistance to first and second-line chemo/radiotherapies. In view of the sterile environment of lung cancer, several immunotherapeutic drugs including nivolumab, pembrolizumab, atezolizumab, and durvalumab are currently being used in clinics globally with the intention of releasing exhausted T-cells back against refractory tumor cells. Immunotherapies have a limited response rate and may cause immune-related adverse events (irAEs) in some patients. Hence, a deeper understanding of regulating immune checkpoint interactions could significantly enhance lung cancer treatments. In this review, we explore the role of miRNAs in modulating immunogenic responses against tumors. We discuss various aspects of how manipulating these checkpoints can bias the immune system’s response against lung cancer. Specifically, we examine how altering the miRNA profile can impact the activity of various immune checkpoint inhibitors, focusing on the PD-1/PD-L1 pathway within the complex landscape of lung cancer. We believe that a clear understanding of the host’s miRNA profile can influence the efficacy of checkpoint inhibitors and significantly contribute to existing immunotherapies for lung cancer patients. Additionally, we discuss ongoing clinical trials involving immunotherapeutic drugs, both as standalone treatments and in combination with other therapies, intending to advance the development of immunotherapy for lung cancer.

Recognizing the need to enhance immune cells' ability to target and eliminate tumor cells by focusing on tumor-associated antigens is crucial for the success of immunotherapy. Numerous cell-based therapies, such as CAR-T cell therapy, tumor-infiltrating lymphocyte (TIL) therapy, CAR-NK cell therapy, and T-cell receptor (TCR)-based therapies, are currently undergoing clinical and pre-clinical evaluation across various cancer types. However, a significant challenge lies in managing the inflammatory responses that are harmful to cancer patients. To overcome this, developing advanced strategies to target tumor cells precisely while preserving immune balance in cancer patients is imperative. One promising approach involves using modified tumor-associated macrophages (TAMs), which constitute approximately 50% of the tumor microenvironment (TME) and play a pivotal role in tumor progression. CAR-Macrophage (CAR-M) therapy is an emerging potential asset of immunotherapy for a wide range of tumors.