Mechanistic insights into circRNA-mediated regulation of PI3K signaling pathway in glioma progression.

Circular RNAs (CircRNAs) are non-coding RNAs (ncRNAs) characterized by a stable circular structure that regulates gene expression at both transcriptional and post-transcriptional levels. They play diverse roles, including protein interactions, DNA methylation modification, protein-coding potential, pseudogene creation, and miRNA sponging, all of which influence various physiological processes. CircRNAs are often highly expressed in brain tissues, and their levels vary with neural development, suggesting their significance in nervous system diseases such as gliomas. Research has shown that circRNA expression related to the PI3K pathway correlates with various clinical features of gliomas. There is an interact between circRNAs and the PI3K pathway to regulate glioma cell processes such as proliferation, differentiation, apoptosis, inflammation, angiogenesis, and treatment resistance. Additionally, PI3K pathway-associated circRNAs hold potential as biomarkers for cancer diagnosis, prognosis, and treatment. In this study, we reviewed the latest advances in the expression and cellular roles of PI3K-mediated circRNAs and their connections to glioma carcinogenesis and progression. We also highlighted the significance of circRNAs as diagnostic and prognostic biomarkers and therapeutic targets in glioma.

Unraveling the molecular landscape of osteoarthritis: A comprehensive review focused on the role of non-coding RNAs.

Osteoarthritis (OA) poses a significant global health challenge, with its prevalence anticipated to increase in the coming years. This review delves into the emerging molecular biomarkers in OA pathology, focusing on the roles of various molecules such as metabolites, noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Advances in omics technologies have transformed biomarker identification, enabling comprehensive analyses of the complex pathways involved in OA pathogenesis. Notably, ncRNAs, especially miRNAs and lncRNAs, exhibit dysregulated expression patterns in OA, presenting promising opportunities for diagnosis and therapy. Additionally, the intricate interplay between epigenetic modifications and OA progression highlights the regulatory role of epigenetics in gene expression dynamics. Genome-wide association studies have pinpointed key genes undergoing epigenetic changes, providing insights into the inflammatory processes and chondrocyte hypertrophy typical of OA. Understanding the molecular landscape of OA, including biomarkers and epigenetic mechanisms, holds significant potential for developing innovative diagnostic tools and therapeutic strategies for OA management.

Ferroptosis contributes to the progression of female-specific neoplasms, from breast cancer to gynecological malignancies in a manner regulated by non-coding RNAs: Mechanistic implications.

Ferroptosis, a recently identified type of non-apoptotic cell death, triggers the elimination of cells in the presence of lipid peroxidation and in an iron-dependent manner. Indeed, ferroptosis-stimulating factors have the ability of suppressing antioxidant capacity, leading to the accumulation of reactive oxygen species (ROS) and the subsequent oxidative death of the cells. Ferroptosis is involved in the pathophysiological basis of different maladies, such as multiple cancers, among which female-oriented malignancies have attracted much attention in recent years. In this context, it has also been unveiled that non-coding RNA transcripts, including microRNAs, long non-coding RNAs, and circular RNAs have regulatory interconnections with the ferroptotic flux, which controls the pathogenic development of diseases. Furthermore, the potential of employing these RNA transcripts as therapeutic targets during the onset of female-specific neoplasms to modulate ferroptosis has become a research hotspot; however, the molecular mechanisms and functional alterations of ferroptosis still require further investigation. The current review comprehensively highlights ferroptosis and its association with non-coding RNAs with a focus on how this crosstalk affects the pathogenesis of female-oriented malignancies, from breast cancer to ovarian, cervical, and endometrial neoplasms, suggesting novel therapeutic targets to decelerate and even block the expansion and development of these tumors.

The function and mechanism of circRNAs in 5-fluorouracil resistance in tumors: Biological mechanisms and future potential.

5-Fluorouracil (5-FU) is a well-known chemotherapy drug extensively used in the treatment of breast cancer. It works by inhibiting cancer cell proliferation and inducing cell death through direct incorporation into DNA and RNA via thymidylate synthase (TS). Circular RNAs (circRNAs), a novel family of endogenous non-coding RNAs (ncRNAs) with limited protein-coding potential, contribute to 5-FU resistance. Their identification and targeting are crucial for enhancing chemosensitivity. CircRNAs can regulate tumor formation and invasion by adhering to microRNAs (miRNAs) and interacting with RNA-binding proteins, regulating transcription and translation. MiRNAs can influence enzymes responsible for 5-FU metabolism in cancer cells, affecting their sensitivity or resistance to the drug. In the context of 5-FU resistance, circRNAs can target miRNAs and regulate biological processes such as cell proliferation, cell death, glucose metabolism, hypoxia, epithelial-to-mesenchymal transition (EMT), and drug efflux. This review focuses on the function of circRNAs in 5-FU resistance, discussing the underlying molecular pathways and biological mechanisms. It also presents recent circRNA/miRNA-targeted cancer therapeutic strategies for future clinical application.

The multifaceted role of SOX2 in breast and lung cancer dynamics.

Breast and lung cancers are leading causes of death among patients, with their global mortality and morbidity rates increasing. Conventional treatments often prove inadequate due to resistance development. The alteration of molecular interactions may accelerate cancer progression and treatment resistance. SOX2, known for its abnormal expression in various human cancers, can either accelerate or impede cancer progression. This review focuses on examining the role of SOX2 in breast and lung cancer development. An imbalance in SOX2 expression can promote the growth and dissemination of these cancers. SOX2 can also block programmed cell death, affecting autophagy and other cell death mechanisms. It plays a significant role in cancer metastasis, mainly by regulating the epithelial-to-mesenchymal transition (EMT). Additionally, an imbalanced SOX2 expression can cause resistance to chemotherapy and radiation therapy in these cancers. Genetic and epigenetic factors may affect SOX2 levels. Pharmacologically targeting SOX2 could improve the effectiveness of breast and lung cancer treatments.

Implications of c-Myc in the pathogenesis and treatment efficacy of urological cancers.

Urological cancers, including prostate, bladder, and renal cancers, are significant causes of death and negatively impact the quality of life for patients. The development and progression of these cancers are linked to the dysregulation of molecular pathways. c-Myc, recognized as an oncogene, exhibits abnormal levels in various types of tumors, and current evidence supports the therapeutic targeting of c-Myc in cancer treatment. This review aims to elucidate the role of c-Myc in driving the progression of urological cancers. c-Myc functions to enhance tumorigenesis and has been documented to increase growth and metastasis in prostate, bladder, and renal cancers. Furthermore, the dysregulation of c-Myc can result in a diminished response to therapy in these cancers. Non-coding RNAs, ß-catenin, and XIAP are among the regulators of c-Myc in urological cancers. Targeting and suppressing c-Myc therapeutically for the treatment of these cancers has been explored. Additionally, the expression level of c-Myc may serve as a prognostic factor in clinical settings.

The science of exosomes: Understanding their formation, capture, and role in cellular communication.

Extracellular vesicles (EVs) serve as a crucial method for transferring information among cells, which is vital in multicellular organisms. Among these vesicles, exosomes are notable for their small size, ranging from 20 to 150 nm, and their role in cell-to-cell communication. They carry lipids, proteins, and nucleic acids between cells. The creation of exosomes begins with the inward budding of the cell membrane, which then encapsulates various macromolecules as cargo. Once filled, exosomes are released into the extracellular space and taken up by target cells via endocytosis and similar processes. The composition of exosomal cargo varies, encompassing diverse macromolecules with specific functions. Because of their significant roles, exosomes have been isolated from various cell types, including cancer cells, endothelial cells, macrophages, and mesenchymal cells, with the aim of harnessing them for therapeutic applications. Exosomes influence cellular metabolism, and regulate lipid, glucose, and glutamine pathways. Their role in pathogenesis is determined by their cargo, which can manipulate processes such as apoptosis, proliferation, inflammation, migration, and other molecular pathways in recipient cells. Non-coding RNA transcripts, a common type of cargo, play a pivotal role in regulating disease progression. Exosomes are implicated in numerous biological and pathological processes, including inflammation, cancer, cardiovascular diseases, diabetes, wound healing, and ischemic-reperfusion injury. As a result, they hold significant potential in the treatment of both cancerous and non-cancerous conditions.

A comprehensive review of the PTEN/PI3K/Akt axis in multiple myeloma: From molecular interactions to potential therapeutic targets.

Phosphatase and tensin homolog (PTEN), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) signaling pathways contribute to the development of several cancers, including multiple myeloma (MM). PTEN is a tumor suppressor that influences the PI3K/Akt/mTOR pathway, which in turn impacts vital cellular processes like growth, survival, and treatment resistance. The current study aims to present the role of PTEN and PI3K/Akt/mTOR signaling in the development of MM and its response to treatment. In addition, the molecular interactions in MM that underpin the PI3K/Akt/mTOR pathway and address potential implications for the development of successful treatment plans are also discussed in detail. We investigate their relationship to both upstream and downstream regulators, highlighting new developments in combined therapies that target the PTEN/PI3K/Akt axis to overcome drug resistance, including the use of PI3K and mitogen-activated protein kinase (MAPK) inhibitors. We also emphasize that PTEN/PI3K/Akt pathway elements may be used in MM diagnosis, prognosis, and therapeutic targets.

Amino acid transporters within the solute carrier superfamily: Underappreciated proteins and novel opportunities for cancer therapy.

BACKGROUND: Solute carrier (SLC) transporters, a diverse family of membrane proteins, are instrumental in orchestrating the intake and efflux of nutrients including amino acids, vitamins, ions, nutrients, etc, across cell membranes. This dynamic process is critical for sustaining the metabolic demands of cancer cells, promoting their survival, proliferation, and adaptation to the tumor microenvironment (TME). Amino acids are fundamental building blocks of cells and play essential roles in protein synthesis, nutrient sensing, and oncogenic signaling pathways. As key transporters of amino acids, SLCs have emerged as crucial players in maintaining cellular amino acid homeostasis, and their dysregulation is implicated in various cancer types. Thus, understanding the intricate connections between amino acids, SLCs, and cancer is pivotal for unraveling novel therapeutic targets and strategies. SCOPE OF REVIEW: In this review, we delve into the significant impact of amino acid carriers of the SLCs family on the growth and progression of cancer and explore the current state of knowledge in this field, shedding light on the molecular mechanisms that underlie these relationships and highlighting potential avenues for future research and clinical interventions. MAJOR CONCLUSIONS: Amino acids transportation by SLCs plays a critical role in tumor progression. However, some studies revealed the tumor suppressor function of SLCs. Although several studies evaluated the function of SLC7A11 and SLC1A5, the role of some SLC proteins in cancer is not studied well. To exert their functions, SLCs mediate metabolic rewiring, regulate the maintenance of redox balance, affect main oncogenic pathways, regulate amino acids bioavailability within the TME, and alter the sensitivity of cancer cells to therapeutics. However, different therapeutic methods that prevent the function of SLCs were able to inhibit tumor progression. This comprehensive review provides insights into a rapidly evolving area of cancer biology by focusing on amino acids and their transporters within the SLC superfamily.

NF-ĸB axis in diabetic neuropathy, cardiomyopathy and nephropathy: A roadmap from molecular intervention to therapeutic strategies.

Diabetes mellitus (DM) is a metabolic illness defined by elevated blood glucose levels, mediating various tissue alterations, including the dysfunction of vital organs. Diabetes mellitus (DM) can lead to many consequences that specifically affect the brain, heart, and kidneys. These issues are known as neuropathy, cardiomyopathy, and nephropathy, respectively. Inflammation is acknowledged as a pivotal biological mechanism that contributes to the development of various diabetes consequences. NF-κB modulates inflammation and the immune system at the cellular level. Its abnormal regulation has been identified in several clinical situations, including cancer, inflammatory bowel illnesses, cardiovascular diseases, and Diabetes Mellitus (DM). The purpose of this review is to evaluate the potential impact of NF-κB on complications associated with DM. Enhanced NF-κB activity promotes inflammation, resulting in cellular harm and compromised organ performance. Phytochemicals, which are therapeutic molecules, can potentially decline the NF-κB level, therefore alleviating inflammation and the progression of problems correlated with DM. More importantly, the regulation of NF-κB can be influenced by various factors, such as TLR4 in DM. Highlighting these factors can facilitate the development of novel therapies in the future.

Circular RNAs in EMT-driven metastasis regulation: modulation of cancer cell plasticity, tumorigenesis and therapy resistance.

The non-coding RNAs comprise a large part of human genome lack of capacity in encoding functional proteins. Among various members of non-coding RNAs, the circular RNAs (circRNAs) have been of importance in the pathogenesis of human diseases, especially cancer. The circRNAs have a unique closed loop structure and due to their stability, they are potential diagnostic and prognostic factors in cancer. The increasing evidences have highlighted the role of circRNAs in the modulation of proliferation and metastasis of cancer cells. On the other hand, metastasis has been responsible for up to 90% of cancer-related deaths in patients, requiring more investigation regarding the underlying mechanisms modulating this mechanism. EMT enhances metastasis and invasion of tumor cells, and can trigger resistance to therapy. The cells demonstrate dynamic changes during EMT including transformation from epithelial phenotype into mesenchymal phenotype and increase in N-cadherin and vimentin levels. The process of EMT is reversible and its reprogramming can disrupt the progression of tumor cells. The aim of current review is to understanding the interaction of circRNAs and EMT in human cancers and such interaction is beyond the regulation of cancer metastasis and can affect the response of tumor cells to chemotherapy and radiotherapy. The onco-suppressor circRNAs inhibit EMT, while the tumor-promoting circRNAs mediate EMT for acceleration of carcinogenesis. Moreover, the EMT-inducing transcription factors can be controlled by circRNAs in different human tumors.

Multifunctional and stimuli-responsive liposomes in hepatocellular carcinoma diagnosis and therapy.

Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer, mainly occurring in Asian countries with an increased incidence rate globally. Currently, several kinds of therapies have been deployed for HCC therapy including surgical resection, chemotherapy, radiotherapy and immunotherapy. However, this tumor is still incurable, requiring novel strategies for its treatment. The nanomedicine has provided the new insights regarding the treatment of cancer that liposomes as lipid-based nanoparticles, have been widely applied in cancer therapy due to their biocompaitiblity, high drug loading and ease of synthesis and modification. The current review evaluates the application of liposomes for the HCC therapy. The drugs and genes lack targeting ability into tumor tissues and cells. Therefore, loading drugs or genes on liposomes can increase their accumulation in tumor site for HCC suppression. Moreover, the stimuli-responsive liposomes including pH-, redox- and light-sensitive liposomes are able to deliver drug into tumor microenvironment to improve therapeutic index. Since a number of receptors upregulate on HCC cells, the functionalization of liposomes with lactoferrin and peptides can promote the targeting ability towards HCC cells. Moreover, phototherapy can be induced by liposomes through loading phtoosensitizers to stimulate photothermal- and photodynamic-driven ablation of HCC cells. Overall, the findings are in line with the fact that liposomes are promising nanocarriers for the treatment of HCC.

Epigenetic regulation of hepatocellular carcinoma progression: MicroRNAs as therapeutic, diagnostic and prognostic factors.

Hepatocellular carcinoma (HCC), a significant challenge for public healthcare systems in developed Western countries including the USA, Canada, and the UK, is influenced by different risk factors including hepatitis virus infections, alcoholism, and smoking. The disruption in the balance of microRNAs (miRNAs) plays a vital function in tumorigenesis, given their function as regulators in numerous signaling networks. These miRNAs, which are mature and active in the cytoplasm, work by reducing the expression of target genes through their impact on mRNAs. MiRNAs are particularly significant in HCC as they regulate key aspects of the tumor, like proliferation and invasion. Additionally, during treatment phases such as chemotherapy and radiotherapy, the levels of miRNAs are key determinants. Pre-clinical experiments have demonstrated that altered miRNA expression contributes to HCC development, metastasis, drug resistance, and radio-resistance, highlighting related molecular pathways and processes like MMPs, EMT, apoptosis, and autophagy. Furthermore, the regulatory role of miRNAs in HCC extends beyond their immediate function, as they are also influenced by other epigenetic factors like lncRNAs and circular RNAs (circRNAs), as discussed in recent reviews. Applying these discoveries in predicting the prognosis of HCC could mark a significant advancement in the therapy of this disease.

Non-coding RNA transcripts, incredible modulators of cisplatin chemo-resistance in bladder cancer through operating a broad spectrum of cellular processes and signaling mechanism.

Bladder cancer (BC) is a highly frequent neoplasm in correlation with significant rate of morbidity, mortality, and cost. The onset of BC is predominantly triggered by environmental and/or occupational exposures to carcinogens, such as tobacco. There are two distinct pathways by which BC can be developed, including non-muscle-invasive papillary tumors (NMIBC) and non-papillary (or solid) muscle-invasive tumors (MIBC). The Cancer Genome Atlas project has further recognized key genetic drivers of MIBC along with its subtypes with particular properties and therapeutic responses; nonetheless, NMIBC is the predominant BC presentation among the suffering individuals. Radical cystoprostatectomy, radiotherapy, and chemotherapy have been verified to be the common therapeutic interventions in metastatic tumors, among which chemotherapeutics are more conventionally utilized. Although multiple chemo drugs have been broadly administered for BC treatment, cisplatin is reportedly the most effective chemo drug against the corresponding malignancy. Notwithstanding, tumor recurrence is usually occurred following the consumption of cisplatin regimens, particularly due to the progression of chemo-resistant trait. In this framework, non-coding RNAs (ncRNAs), as abundant RNA transcripts arise from the human genome, are introduced to serve as crucial contributors to tumor expansion and cisplatin chemo-resistance in bladder neoplasm. In the current review, we first investigated the best-known ncRNAs, i.e. microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), correlated with cisplatin chemo-resistance in BC cells and tissues. We noticed that these ncRNAs could mediate the BC-related cisplatin-resistant phenotype through diverse cellular processes and signaling mechanisms, reviewed here. Eventually, diagnostic and prognostic potential of ncRNAs, as well as their therapeutic capabilities were highlighted in regard to BC management.

Harnessing function of EMT in cancer drug resistance: a metastasis regulator determines chemotherapy response.

Epithelial-mesenchymal transition (EMT) is a complicated molecular process that governs cellular shape and function changes throughout tissue development and embryogenesis. In addition, EMT contributes to the development and spread of tumors. Expanding and degrading the surrounding microenvironment, cells undergoing EMT move away from the main location. On the basis of the expression of fibroblast-specific protein-1 (FSP1), fibroblast growth factor (FGF), collagen, and smooth muscle actin (-SMA), the mesenchymal phenotype exhibited in fibroblasts is crucial for promoting EMT. While EMT is not entirely reliant on its regulators like ZEB1/2, Twist, and Snail proteins, investigation of upstream signaling (like EGF, TGF-ß, Wnt) is required to get a more thorough understanding of tumor EMT. Throughout numerous cancers, connections between tumor epithelial and fibroblast cells that influence tumor growth have been found. The significance of cellular crosstalk stems from the fact that these events affect therapeutic response and disease prognosis. This study examines how classical EMT signals emanating from various cancer cells interfere to tumor metastasis, treatment resistance, and tumor recurrence.

Biological landscape and nanostructural view in development and reversal of oxaliplatin resistance in colorectal cancer.

The treatment of cancer patients has been mainly followed using chemotherapy and it is a gold standard in improving prognosis and survival rate of patients. Oxaliplatin (OXA) is a third-platinum anti-cancer agent that reduces DNA synthesis in cancer cells to interfere with their growth and cell cycle progression. In spite of promising results of using OXA in cancer chemotherapy, the process of drug resistance has made some challenges. OXA is commonly applied in treatment of colorectal cancer (CRC) as a malignancy of gastrointestinal tract and when CRC cells increase their proliferation and metastasis, they can obtain resistance to OXA chemotherapy. A number of molecular factors such as CHK2, SIRT1, c-Myc, LATS2 and FOXC1 have been considered as regulators of OXA response in CRC cells. The non-coding RNAs are able to function as master regulator of other molecular pathways in modulating OXA resistance. There is a close association between molecular mechanisms such as apoptosis, autophagy, glycolysis and EMT with OXA resistance, so that apoptosis inhibition, pro-survival autophagy induction and stimulation of EMT and glycolysis can induce OXA resistance in CRC cells. A number of anti-tumor compounds including astragaloside IV, resveratrol and nobiletin are able to enhance OXA sensitivity in CRC cells. Nanoparticles for increasing potential of OXA in CRC suppression and reversing OXA resistance have been employed in cancer chemotherapy. These subjects are covered in this review article to shed light on molecular factors resulting in OXA resistance.

EZH2 as a potential therapeutic target for gastrointestinal cancers.

Gastrointestinal (GI) cancers continue to be a major cause of mortality and morbidity globally. Understanding the molecular pathways associated with cancer progression and severity is essential for creating effective cancer treatments. In cancer research, there is a notable emphasis on Enhancer of zeste homolog 2 (EZH2), a key player in gene expression influenced by its irregular expression and capacity to attach to promoters and alter methylation status. This review explores the impact of EZH2 signaling on various GI cancers, such as colorectal, gastric, pancreatic, hepatocellular, esophageal, and cholangiocarcinoma. The primary function of EZH2 signaling is to facilitate the accelerated progression of cancer cells. Additionally, EZH2 has the capacity to modulate the reaction of GI cancers to chemotherapy and radiotherapy. Numerous pathways, including long non-coding RNAs and microRNAs, serve as upstream regulators of EZH2 in these types of cancer. EZH2's enzymatic activity enables it to attach to target gene promoters, resulting in methylation that modifies their expression. EZH2 could be considered as an independent prognostic factor, with increased expression correlating with a worse disease prognosis. Additionally, a range of gene therapies including small interfering RNA, and anti-tumor agents are being explored to target EZH2 for cancer treatment. This comprehensive review underscores the current insights into EZH2 signaling in gastrointestinal cancers and examines the prospect of therapies targeting EZH2 to enhance patient outcomes.

Pathological roles of miRNAs and pseudogene-derived lncRNAs in human cancers, and their comparison as prognosis/diagnosis biomarkers.

This review examines and compares the diagnostic and prognostic capabilities of miRNAs and lncRNAs derived from pseudogenes in cancer patients. Additionally, it delves into their roles in cancer pathogenesis. Both miRNAs and pseudogene-derived lncRNAs have undergone thorough investigation as remarkably sensitive and specific cancer biomarkers, offering significant potential for cancer detection and monitoring. . Extensive research is essential to gain a complete understanding of the precise roles these non-coding RNAs play in cancer, allowing the development of novel targeted therapies and biomarkers for improved cancer detection and treatment approaches.

Role of non-coding RNAs in osteoporosis.

Osteoporosis, a prevalent bone disorder influenced by genetic and environmental elements, significantly increases the likelihood of fractures and bone weakness, greatly affecting the lives of those afflicted. Yet, the exact epigenetic processes behind the onset of osteoporosis are still unclear. Growing research indicates that epigenetic changes could act as vital mediators that connect genetic tendencies and environmental influences, thereby increasing the risk of osteoporosis and bone fractures. Within these epigenetic factors, certain types of RNA, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been recognized as key regulatory elements. These RNA types wield significant influence on gene expression through epigenetic regulation, directing various biological functions essential to bone metabolism. This extensive review compiles current research uncovering the complex ways in which miRNAs, lncRNAs, and circRNAs are involved in the development of osteoporosis, especially in osteoblasts and osteoclasts. Gaining a more profound understanding of the roles these three RNA classes play in osteoporosis could reveal new diagnostic methods and treatment approaches for this incapacitating condition. In conclusion, this review delves into the complex domain of epigenetic regulation via non-coding RNA in osteoporosis. It sheds light on the complex interactions and mechanisms involving miRNAs, lncRNAs, and circRNAs within osteoblasts and osteoclasts, offering an in-depth understanding of the less explored aspects of osteoporosis pathogenesis. These insights not only reveal the complexity of the disease but also offer significant potential for developing new diagnostic methods and targeted treatments. Therefore, this review marks a crucial step in deciphering the elusive complexities of osteoporosis, leading towards improved patient care and enhanced quality of life.

miRNAs and exosomal miRNAs in lung cancer: New emerging players in tumor progression and therapy response.

Non-coding RNAs have shown key roles in cancer and among them, short RNA molecules are known as microRNAs (miRNAs). These molecules have length less than 25 nucleotides and suppress translation and expression. The functional miRNAs are produced in cytoplasm. Lung cancer is a devastating disease that its mortality and morbidity have undergone an increase in recent years. Aggressive behavior leads to undesirable prognosis and tumors demonstrate abnormal proliferation and invasion. In the present review, miRNA functions in lung cancer is described. miRNAs reduce/increase proliferation and metastasis. They modulate cell death and proliferation. Overexpression of oncogenic miRNAs facilitates drug resistance and radio-resistance in lung cancer. Tumor microenvironment components including macrophages and cancer-associated fibroblasts demonstrate interactions with miRNAs in lung cancer. Other factors such as HIF-1α, lncRNAs and circRNAs modulate miRNA expression. miRNAs have also value in the diagnosis of lung cancer. Understanding such interactions can pave the way for developing novel therapeutics in near future for lung cancer patients.