Deciphering the role of MitomiRs in cancer: A comprehensive review.

MicroRNAs (miRNAs) are short non-coding RNAs that regulate many metabolic and signal transduction pathways. The role of miRNAs, usually found in the cytoplasm, in regulating gene expression and cancer progression has been extensively studied in the last few decades. However, very recently, miRNAs were found to localize in the mitochondria. MiRNAs that specifically localize in the mitochondria and the cytoplasmic miRNAs associated with mitochondria that directly or indirectly modulate specific mitochondrial functions are termed as "mitomiRs". Although it is not clear about the origin of mitomiRs that are situated within mitochondria (nuclear or mitochondrial origin), it is evident that they have specific functions in modulating gene expression and regulating important mitochondrial metabolic pathways. Through this review, we aim to delineate the mechanisms by which mitomiRs alter mitochondrial metabolic pathways and influence the initiation and progression of cancer. We further discuss the functions of particular mitomiRs, which have been widely studied in the context of mitochondrial metabolism and oncogenic signaling pathways. Based on the current knowledge, we can conclude that mitomiRs contribute significantly to mitochondrial function and metabolic regulation, and that dysregulation of mitomiRs can aid the proliferation of cancer cells. Therefore, the less explored area of mitomiRs' biology can be an important topic of research investigation in the future for targeting cancer cells.

The role of tumor-educated platelets in ovarian cancer: A comprehensive review and update.

Platelets have recently surfaced as critical players in cancer metastasis and the local and systemic responses to tumor growth. The emerging concept of "Tumor-educated platelets (TEPs)" comprises the exchange of biomolecules between tumor cells and platelets, thereby leading to the "education" of platelets. Increased platelet numbers have long been associated with cancer patients' tumor metastasis and poor clinical prognosis. However, it is very recently that researchers have delved deeper into the tumor-microenvironment and probed the mechanism of interactions between tumor cells and platelets. Designing strategies to target the TEPs and the communications between platelets and tumor cells can prove to be a promising breakthrough in cancer therapy. Through this review, we aim to analyze the recent developments in this field and discuss the characteristics of TEPs, focusing on ovarian cancer-associated TEPs and their characteristics, the interplay between ovarian cancer-associated TEPs and cancer cells, and the purview of TEP-targeted cancer diagnosis and therapy, including platelet biomarkers and inhibitors.

Current Update on Nanotechnology-Based Approaches in Ovarian Cancer Therapy.

Ovarian cancer is one of the leading causes of cancer-related deaths among women. The drawbacks of conventional therapeutic strategies encourage researchers to look for alternative strategies, including nanotechnology. Nanotechnology is one of the upcoming domains of science that is rechanneled towards targeted cancer therapy and diagnosis. Nanocarriers such as dendrimers, liposomes, polymer micelles, and polymer nanoparticles present distinct surface characteristics in morphology, surface chemistry, and mode of action that help differentiate normal and malignant cells, which paves the way for target-specific drug delivery. Similarly, nanoparticles have been strategically utilized as efficacious vehicles to deliver drugs that alter the epigenetic modifications in epigenetic therapy. Some studies suggest that the use of specialized target-modified nanoparticles in siRNA-based nanotherapy prevents internalization and improves the antitumor activity of siRNA by ensuring unrestrained entry of siRNA into the tumor vasculature and efficient intracellular delivery of siRNA. Moreover, research findings highlight the significance of utilizing nanoparticles as depots for photosensitive drugs in photodynamic therapy. The applicability of nanoparticles is further extended to medical imaging. They serve as contrast agents in combination with conventional imaging modalities such as MRI, CT, and fluorescence-based imaging to produce vivid and enhanced images of tumors. Therefore, this review aims to explore and delve deeper into the advent of various nanotechnology-based therapeutic and imaging techniques that provide non-invasive and effective means to tackle ovarian cancers.

Landscape of Clinically Relevant Exosomal tRNA-Derived Non-coding RNAs.

Exosomes are extra-cellular vesicles that are < 150 nm that is formed by invagination of the plasma membrane and are released as vesicles. These contain proteins, RNA, and DNA as their cargo. In recent times, the non-coding RNA (ncRNA) present within exosomes has been studied extensively in the context of sorting, localization, and their potential as biomarkers. For example, miR-1246, miR-1290, miR-21, and miR-23a are exosomal biomarkers of cancer, and YBX1 (Y-Box Binding Protein 1) is attributed to exosomal RNA sorting. Transfer RNA-derived fragments are a class of small ncRNAs that were discovered in 2009. They are classified as tRFs (tRNA-derived fragments) and tsRNAs (tRNA halves). Interestingly, these tRNA-derived ncRNAs are emerging as biomarkers in various diseases, and these are found in exosomes. To date, the literature has covered only the biomarker potential of plasma/serum tRNA-derived ncRNAs. Hence, in the current review, we discuss the exosomal tRNA-derived fragments that are clinically relevant in pathological conditions.

Breast cancer fibroblasts and cross-talk.

The breast tumor microenvironment is one of the crucial elements supporting breast cancer tumor progression and metastasis. The fibroblasts are the chief cellular component of the stromal microenvironment and are pathologically activated and differentiated into breast cancer-associated fibroblasts (CAFs). The catabolic phenotype of breast CAFs arises due to metabolic reprogramming of these fibroblasts under pseudo-hypoxic conditions. The metabolic intermediates and ATP produced by the breast CAFs are exploited by the neighboring cancer cells for energy generation. The growth factors, cytokines, and chemokines secreted by the CAFs help fuel tumor growth, invasion, and dissemination. Moreover, the interplay between breast CAFs and cancer cells, mediated by the growth factors, ROS, metabolic intermediates, exosomes, and catabolite transporters, aids in building a favorable microenvironment that promotes cancer cell proliferation, tumor progression, and metastasis. Therefore, identifying effective means to target the reprogrammed metabolism of the breast CAFs and the cross-communication between CAFs and cancer cells serve as promising strategies to develop anti-cancer therapeutics. Henceforth, the scope of the present review ranges from discussing the underlying characteristics of breast CAFs, mechanisms of metabolic reprogramming in breast CAFs, and the nature of interactions between breast CAFs and cancer cells to studying the intricacies of reprogrammed metabolism targeted cancer therapy.

Long Non-coding RNA NEAT1 as an Emerging Biomarker in Breast and Gynecologic Cancers: a Systematic Overview.

Long non-coding RNAs (lncRNAs) are emerging regulators of cellular pathways, especially in cancer development. Among the lncRNAs, nuclear paraspeckle assembly transcript 1 (NEAT1) forms a scaffold for a nuclear body; the paraspeckle and aberrant expression of NEAT1 have been reported in breast and gynecologic cancers (ovarian, cervical, endometrial, and vulvar). Abundantly expressed NEAT1 in breast and gynecologic cancers generally contribute to tumor development by sponging its corresponding tumor-suppressive microRNAs or interacting with various regulatory proteins. The distinct expression of NEAT1 and its contribution to tumorigenic pathways make it a promising therapeutic target in breast and gynecologic cancers. Herein, we summarize the functions and molecular mechanisms of NEAT1 in human breast, ovarian, cervical, endometrial, and vulvar cancers. Furthermore, we emphasize its critical role in the formation of paraspeckle development and its functions. Conclusively, NEAT1 is a considerable biomarker with a bright prospect and can be therapeutically targeted to manage breast and gynecologic cancers.

Liquid biopsy in ovarian cancer.

Ovarian cancer is typically diagnosed at an advanced stage and poses a significant challenge to treatment and recovery. Relapsed ovarian cancer and chemoresistance of ovarian tumor cells are other clinical challenges. Liquid biopsy is an essential non-invasive diagnostic test that evaluates circulating tumor cells and tumor DNA, as well as other blood markers that may be useful in guiding precision medicine. Although liquid biopsy is not a routinely used diagnostic test, the potential applications in the diagnosis and prognosis in ovarian cancer are rapidly growing. This review explores recent studies examining the clinical potential of circulating tumor cells, cell-free microRNA, exosomes, tumor DNA, and other analytes as a source of liquid biopsy biomarkers in ovarian cancer diagnosis, prognosis and response to treatment.

Folic acid conjugation improves the bioavailability and chemosensitizing efficacy of curcumin-encapsulated PLGA-PEG nanoparticles towards paclitaxel chemotherapy.

Nanoencapsulation has emerged as a novel strategy to enhance the pharmacokinetic and therapeutic potential of conventional drugs. Recent studies from our lab have established the efficacy of curcumin in sensitizing cervical cancer cells and breast cancer cells towards paclitaxel and 5-FU chemotherapy respectively. Factors that hinder the clinical use of curcumin as a sensitizer or therapeutic agent include its poor bioavailability and retention time. Earlier reports of improvement in bioavailability and retention of drugs upon nanoencapsulation have motivated us in developing various nanoformulations of curcumin, which were found to exhibit significant enhancement in bioavailability and retention time as assessed by our previous in vitro studies. Among the various formulations tested, curcumin-entrapped in PLGA-PEG nanoparticles conjugated to folic acid (PPF-curcumin) displayed maximum cell death. In the present study, we have demonstrated the efficacy of this formulation in augmenting the bioavailability and retention time of curcumin, in vivo, in Swiss albino mice. Further, the acute and chronic toxicity studies proved that the formulation is pharmacologically safe. We have also evaluated its potential in chemosensitizing cervical cancer cells to paclitaxel and have verified the results using cervical cancer xenograft model in NOD-SCID mice. Folic acid conjugation significantly enhanced the efficacy of curcumin in down-regulating various survival signals induced by paclitaxel in cervical cancer cells and have considerably improved its potential in inhibiting the tumor growth of cervical cancer xenografts. The non-toxic nature coupled with improved chemosensitization potential makes PPF-curcumin a promising candidate formulation for clinical trials.