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Background: It is well known that the changes in the expression level of LncRNA can affect the progression of tumors, which has caused a great upsurge of research in recent years. Several LncRNAs have been identified to affect a series of cancers and can promote tumor growth, migration, and invasion. In this review, we aim to clarify the pathophysiological functions of LncRNA MIR4435-2 HG in multiple tumors. Methods: By searching the literature through PubMed, this paper summarizes the relationship between MIR4435-2HG and tumor and its role in the occurrence and development of cancer and also explains the specific molecular mechanism of the effect of MIR4435-2HG on cancer. Results: MIR4435-2HG can function as an oncogene in a variety of cancers. The expression level was reported to be abnormally elevated in a series of cancers, consisting of melanoma, gastric cancer, head and neck squamous cell carcinoma, oral squamous cell carcinoma, lung cancer, cervical cancer, prostate carcinoma, ovarian cancer, breast cancer, hepatocellular carcinoma, clear cell renal cell carcinoma malignant, glioma, and colorectal cancer. Moreover, MIR4435-2HG is related to the poor prognosis of a variety of cancers. MIR4435-2HG can also affect tumor proliferation, invasion, and apoptosis. In addition, MIR4435-2HG can also enhance the metabolic function of myeloid dendritic cells of elite HIV-1 controllers. Conclusion: MIR4435-2HG affects the development of a variety of cancers. It can act as a clinical marker for early tumor diagnosis and affects tumor-targeted therapy.

Abstract: Long non-coding RNA (lncRNA) is a new kind of RNA with a length of over 200 nucleotides. Current frontiers revealed that lncRNAs implicate in various tumor progression, including tumorigenesis, proliferation, migration, invasion, metastasis, and angiogenesis. Recently discovered long non-coding RNA SETbinding factor 2 antisense RNA 1 (lncRNA SBF2-AS1), an oncogenic antisense RNA to SBF2, locates at 11p15.1 locus and is 2708 nt long. Accumulating evidence has demonstrated that lncRNA SBF2-AS1 participates in the progression of the various tumor, including pathogenesis, diagnosis, treatment, and prognosis of acute myeloid leukemia (AML), breast cancer (BC), cervical cancer (CC), clear cell renal cell carcinoma (ccRCC), colorectal cancer (CRC), diffuse large B-cell lymphoma (DLBCL), esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), glioma, glioblastoma (GBM), hepatocellular carcinoma (HCC), lung cancer (LC), lung adenocarcinoma (LUAD), non-small cell lung cancer (NSCLC), osteosarcoma (OS), pancreatic cancer (PC), papillary thyroid cancer (PTC), small cell lung cancer (SCLC). Therefore, we summarized the underlying mechanisms of lncRNA SBF2-AS1 in various cancers to utilize its therapeutic function in target-selective treatment modalities.

Background: FER-1 family member 4 (FER1L4), a 6.7 kb lncRNA located at 20q11.22, plays an important biological function in a variety of tumor diseases. The purpose of this review is to clarify the pathophysiological mechanism and potential biological function of FER1L4 in different tumors. Methods: By searching the relevant literature in PubMed, the specific pathophysiological mechanism of FER1L4 in different tumors was summarized. Results: LncRNA FER1L4 is one of the key factors in tumorigenesis and is abnormally down-regulated in many tumors, including osteosarcoma, lung cancer, laryngeal squamous cell carcinoma, laryngeal cancer, colorectal cancer, ovarian cancer, prostate cancer, esophageal cancer, gastric cancer, endometrial cancer, osteoarthritis, rheumatoid arthritis, and so on. However, FER1L4 is downregulated in breast cancer, glioma, oral squamous cell carcinoma, renal clear cell carcinoma, and periodontitis, and plays a protective role in orthodontic teeth. In addition, as a tumor suppressor gene or oncogene, FER1L4 affects tumor proliferation, invasion, migration, and apoptosis. Conclusion: LncRNA FER1L4 has a good application prospect in the treatment and diagnosis of various tumors.

Abstract: Aging refers to a natural process and a universal phenomenon in all cells, tissues, organs, and the whole organism. Long non-coding RNAs (lncRNAs) are non-coding RNAs with a length of 200 nucleotides. LncRNA growth arrest-specific 5 (lncRNA GAS5) is often down-regulated in cancer. The accumulation of lncRNA GAS5 has been found to be able to inhibit cancer growth, invasion, and metastasis while enhancing the sensitivity of cells to chemotherapy drugs. LncRNA GAS5 can be a signaling protein, which is specifically transcribed under different triggering conditions. Subsequently, it is involved in signal transmission in numerous pathways as a signal node. LncRNA GAS5, with a close relationship to multiple miRNAs, was suggested to be involved in the signaling pathway under three action modes (i.e., signal, bait, and guidance). LncRNA GAS5 was found to be involved in different age-related diseases (e.g., rheumatoid arthritis, type 2 diabetes, atherosclerosis, osteoarthritis, osteoporosis, multiple sclerosis, cancer, etc.). This study mainly summarized the regulatory effect exerted by lncRNA GAS5 on age-related diseases.

Abstract: LncRNA MIR17HG, located at chromosome 13q31, plays an inevitable role in promoting tumor progressions, such as tumorigenesis, proliferation, and metastasis. Besides, lncRNA MIR17HG is rare due to its open reading frame (ORF), which can be translated to produce protein. By systematically retrieval, we summarized that MIR17HG is an emerging lncRNA that exhibits carcinogenically in osteosarcoma (OS), glioma, cervical squamous cell carcinoma (CSCC), colorectal cancer (CRC), gastric cancer (GC), atypical teratoid rhabdoid tumors (ATRT). Furthermore, a high expression level of MIR17HG protein is also linked with meningioma. Additionally, MIR17HG polymorphisms in glioma, CRC, liver cancer (LC), breast cancer (BC), head and neck squamous cell carcinoma (HNSCC), and multiple myeloma (MM) also have a large influence on cancer susceptibility, prognosis, and so on. Collectively, long non-coding RNA MIR17HG’s tumor-stimulative role could be a promising therapeutic target. Besides, by investigating patients’ MIR17HG single-nucleotide polymorphisms (SNPs), clinicians could also personalize the productive interventions in gene therapy or predict the diagnosis/prognosis precisely.

Background: Nuclear‐enriched abundant transcript 1 (abbreviated as NEAT1) is a long-chain noncoding RNA involved in various physiological and pathological processes. This study aimed to clarify the effect and molecule system of NEAT1 within non-alcoholic fatty liver disease (NAFLD) as well as type 2 diabetes (T2DM). Method: In this review, current studies concerning mechanisms of NEAT1l, in the development of type 2 diabetes and its complications have been summarized and analyzed. Also, we searched the papers based on NEAT1 related to NAFLD. The related studies were obtained through a systematic search of Pubmed. Results: NEAT1 displays a close correlation with how T2DM occurs and develops, and it was confirmed to be significantly up-regulated in T2DM and its various complications (e.g., diabetics nephropathy, diabetics cardiomyopathy, diabetics retinopathy as well as diabetic neuropathy). Besides, NEAT1 is capable of impacting the occurrence, development and prognosis of NAFLD and T2DM. Conclusion: LncRNA NEAT1 is likely to act as a novel therapeutic target for T2DM and its complications. Moreover, non-alcoholic fatty liver disease is also correlated with NEAT1.

Background: Increasing academic efforts have been made to explore the correlation of long noncoding RNAs (lncRNAs) with human diseases, particularly metabolic diseases like diabetes mellitus. Taking lncRNA H19 as an example, this review intends to reveal the functions and mechanism of lncRNA H19 in diabetes mellitus and diabetic complications. Methods: The research results associated with lncRNA H19 and diabetes mellitus are collected and summarized on PubMed. Conclusion: LncRNA H19 is a potential instructive marker for the treatment of diabetes mellitus and diabetic complications.

Background: Experimental evidence has shown that lncRNA MALAT1 is related to proliferation ability, invasion and migration ability, autophagy ability, and chemoresistance in gastric cancer. Moreover, MALAT1 is related to metastasis and patient prognosis in gastric cancer. This review aims to reveal the biological functions and specific mechanisms of MALAT1 in gastric cancer. Methods: After a comprehensive and systematic search in PubMed, various molecular mechanisms of MALAT1 in mediating gastric carcinogenesis are collated and summarized. Results: MALAT1-mediated gastric cancer is involved in a variety of molecular mechanisms. For example, MALAT1 can enhance the proliferation ability of gastric cancer cells by inhibiting the expressions of miR-122, miR-1297, miR-22-3p, miR-202, etc. MALAT1 enhances the metastasis and invasion of gastric cancer by participating in the EMT process, PI3-Akt and other pathways. MALAT1 enhances the proliferation and invasion of gastric cancer by inhibiting the function of the tumor suppressor gene PCDH10. MALAT1 can increase the autophagy ability of gastric cancer cells by inhibiting miR-183 and increasing the level of autophagy markers. MALAT1 enhances chemical resistance by inhibiting UPF1 and miR-30e levels. Conclusions: MALAT1 is tightly linked to gastric carcinogenesis through various molecular mechanisms. Moreover, MALAT1 is also closely associated with chemoresistance and poor prognosis in gastric cancer patients, suggesting the possibility of its use as a clinical therapeutic target and a promising independent risk factor for predicting patient prognosis.

Background: It is substantiated that LncRNAs are associated with carcinoma progression. OIP5- AS1 is a tumor-related carcinoma suppressor lncRNA, previously discovered in zebrafish, which is involved in the progression of a variety of cancers, has a regulatory effect on carcinoma, and interacts with miRNA and other biomolecules to affect the physiological and pathological processes of carcinoma cells. This article will discuss the effect of OIP5-AS1 in various cancers and its regulatory mechanism. Methods: This paper summarized and analyzed OIP5-AS1, which functions on the germination and progression of carcinoma and its regulatory mechanism. Meanwhile, the related research was retrieved and collected by the PubMed system. Results: OIP5-AS1 is overexpressed in various tumors, which regulates and controls tumor growth and participates in tumor progression, including breast carcinoma, ovarian carcinoma, cervical carcinoma, lung carcinoma, laryngeal squamous cell gastric carcinoma and hepatocellular carcinoma. The research evidence proves that OIP5-AS1 takes part in carcinoma proliferation, growth, migration, invasion, and apoptosis. Conclusion: OIP5-AS1 probably can be an effective biomarker or a potential therapeutic target in multiple tumors.

Background: Long non-coding RNAs (lncRNAs) has no protein-coding potential due to the lack of an apparent open reading frame. There is growing evidence that lncRNA DGCR5 has a vital regulatory role in human illnesses' pathological development, particularly in the digestive system's carcinogenesis and progression. Abnormal DGCR5 expression affects different cellular functions such as proliferation, aggression, and metastasis. This paper aims to probe into the pathophysiological functions and molecular mechanisms of DGCR5 in cancers of the digestive system. Methods: This review summarizes and analyzes the biological functions and mechanisms of lncRNA DGCR5 in digestive system cancers occurrence. Relevant studies were conducted and reviewed by searching PubMed for articles with lncRNA DGCR5 and digestive system cancer as keywords in recent years. Results: DCGR5, as a novel tumor-related lncRNA, is recently identified to be abnormally expressed in digestive system cancers, such as pancreatic ductal adenocarcinoma, pancreatic cancer, gastric cancer, gallbladder cancer, colorectal cancer, and hepatocellular carcinoma. The role played by DCGR5 is vital and varies in different digestive cancers. Taken together, aberrant expression of DCGR5 regulates the progression of digestive cancers by affecting cancer cell proliferation, aggression, metastasis, and drug resistance. Conclusion: LncRNA DGCR5 might be a viable marker or a promising therapeutic target in digestive system cancers.

Background: Long noncoding RNA (lncRNA) fetal-lethal non-coding developmental regulatory RNA (FENDRR), a newly known lncRNA, has been reported to be abnormally expressed in diverse tumors. This review is focused on clarifying the mechanism of FENDRR to regulate the biological process of tumors, affirming its value as a target for tumor therapy. Methods: The pathophysiological mechanism of FENDRR acting on tumors has been analyzed and summarized by reviewing PubMed. Results: The expression of lncRNA FENDRR is abnormally altered in clinical cancers, promoting the malignant transformation of a variety of tumors, including colon cancer, cervical cancer, hepatocellular carcinoma, prostate cancer, Malignant melanoma, lung cancer, osteosarcoma, breast cancer, etc. Cellular processions, including proliferation, invasion, apoptosis and migration affected by FENDRR, have been revealed. Conclusion: Specific evidences for the involvement of LncRNA FENDRR in cancer regulatory processes suggest that FENDRR has the potential to be a biomarker or clinical therapeutic target for malignant tumors.

Background: Long non-coding RNA (lncRNA) with little or no coding ability has shown a variety of biological functions in cancer, including epigenetic regulation, DNA damage, regulation of microRNAs, and participation in signal transduction pathways. LncRNA can be used as an oncogene and tumor suppressor gene through transcriptional regulation in cancer. For example, the over-expressed lncRNA DLEU2 promotes the occurrence of laryngeal cancer, lung cancer, hepatocellular carcinoma, etc., and inhibits the progression of chronic lymphocytic leukemia. Deleted in Lymphocytic Leukemia 2 (DLEU2), as one of the long non-coding RNAs, was first found in chronic lymphoblastic leukemia and drawn into the progress of innumerable cancers. The molecular mechanism of DLEU2 in multiple tumors will be revealed. Methods: In this review, current studies on the biological functions and mechanisms of DLEU2 in tumors are summarized and analyzed; related researches are systematically retrieved and collected through PubMed. Results: DLEU2, a novel cancer-related lncRNA, has been demonstrated to be abnormally expressed in various malignant tumors, including leukemia, esophageal cancer, lung cancer, glioma, hepatocellular carcinoma, malignant pleural mesothelioma, bladder cancer, pancreatic cancer, pharynx and throat cancer, renal clear cell carcinoma, breast cancer, osteosarcoma. Besides, lncRNA DLEU2 has been shown to be involved in the process of proliferation, migration, invasion and inhibition of apoptosis of cancer cells. Conclusion: Due to the biological functions and mechanisms involved in DLEU2, it may represent an available biomarker or potential therapeutic target in a variety of malignant tumors.

Myocardial infarction (MI) is a frequent outcome of coronary artery disease (CAD) and the key factor contributing to worldwide disability and death. Genetic factors contribute to the pathogenesis of CAD/MI, and SNP rs6903956 in the ADTRP gene was first found associated with CAD/MI in the Chinese Han population, which was successfully replicated in other cohorts. However, whether rs6903956 is a functional SNP and its risk mechanism to CAD/MI remains unknown. The ADTRP gene-encoded androgen-dependent TFPI regulating protein regulates vascular endothelial cell function, endothelial-monocyte adhesion, and thrombosis. The allele A of rs6903956, in particular, is associated with lower ADTRP mRNA levels in lymphocytes. In the current study, we found that SNP rs6903956 exhibits allelic differences in transcriptional activity by interacting with GATA2. Also, the A allele conferred a greater risk of CAD and MI, lowered transcriptional activity, and GATA2 binding ability as compared to the G allele. Our findings provide details on how rs6903956 regulates the expression of ADTRP and may provide novel insights into CAD pathology and susceptibility.

Background: There is increasing evidence that lncRNA, a type of transcript that is over 200 nucleotides in length and may serve as oncogenes or suppressor genes, is implicated in the pathophysiology of human diseases. In particular, tumorigenesis and progress are closely correlated with its abnormal expression. In addition, it may become a promising target for many oncology biotherapies. Abnormal DLX6-AS1 expression affects different cellular processes such as proliferation, aggression and metastasis. This review aims to probe into the pathophysiological functions and molecular mechanisms of DLX6-AS1 in various cancers. Methods: By retrieving the literature, this review summarizes the biological function and mechanism of LncRNA DLX6-AS1 in tumor occurrence. Results: The lncRNA DLX6-AS1 is a new tumor-related RNA that has recently been found to be aberrantly expressed in diverse cancers, such as pancreatic cancer, osteosarcoma, non-small cell lung cancer, gastric carcinoma, glioma, hepatocellular cancer, colorectal carcinoma, renal carcinoma, esophageal squamous cell cancer, ovarian cancer, Ewing sarcoma, cervical cancer, breast cancer, thyroid cancer, neuroblastoma, pulmonary adenocarcinoma, nasopharyngeal carcinoma, squamous laryngeal cancer and bladder cancer, etc. Meanwhile, it is identified that DLX6-AS1 regulates the aggression, translocation and proliferation of diverse cancers. Conclusion: LncRNA DLX6-AS1 may be viable markers in tumors or a potential therapeutic target for multiple tumors.

Background: Long non-coding RNAs (LncRNAs), with the length of over 200 nucleotides, that originate from intergenic, antisense, or promoter-proximal regions, are a large family of RNAs that lack coding capacity. Emerging evidences illustrated that LncRNAs played significant roles in a variety of cellular functions and biological processes in profuse human diseases, especially in cancers. Cancer susceptibility candidate 9 (CASC9), as a member of the LncRNAs group, firstly found its oncogenic function in esophageal cancer. In the following recent studies, a growing amount of human malignancies are verified to be correlated with CASC9, most of which are derived from the squamous epithelium tissue. This present review attempts to highlight the latest insights into the expression, functional roles, and molecular mechanisms of CASC9 in different human malignancies. Methods: In this review, the latest findings related to the pathophysiological processes of CASC9 in human cancers were summarized and analyzed, and the associated studies collected in systematic retrieval of PubMed used lncRNA and CASA9 as keywords. Results: CASC9 expression is identified to be aberrantly elevated in a variety of malignancies. The over-expression of CASC9 has been suggested to accelerate cell proliferation, migration, cell growth and drug resistance of cancer cells, while depressing cell apoptosis, revealing its role as an oncogene. Moreover, the current review demonstrated CASC9 as closely related to the neoplastic transformation of squamous epithelial cells and squamous metaplasia in non-squamous epithelial tissues. Finally, we discuss the limitations and tremendous diagnostic/ therapeutic potential of CASC9 in various human cancers. Conclusion: Long non-coding RNA CASC9 likely serve as useful disease biomarkers or therapeutic targets which be effectively applied in the treatment of different kinds of cancers.

Renal interstitial fibrosis (RIF) is a crucial pathological change leading to chronic kidney disease (CKD). Currently, no effective medicines have been available for treating it. In our research, we examined the effects of polysaccharides extracted from Balanophora polyandra Griff (BPPs) on kidney fibrosis and epithelial to mesenchymal transition (EMT) in vivo and in vitro, aiming to explore the underlying mechanisms. By using the mice with unilateral urethral obstruction (UUO) as experimental subjects, we examined the medicinal values of BPPs on alleviating RIF. The effects of BPPs were evaluated by examining the histological staining and relative mRNA and protein expression levels of the related genes. The possible underlying mechanisms were further explored with human normal renal proximal tubular epithelia (HK‐2 cells) as in vitro model. In UUO mice, BPP treatment could significantly alleviate interstitial fibrosis through reducing the components (Collagens I, III and IV) of extracellular matrix (ECM), and reducing the activation of fibroblasts producing these components, as revealed by inhibiting the hallmarks (fibronectin and α‐SMA) of fibroblast activation. Furthermore, BPP administration increased the expression levels of matrix metalloproteinases (MMPs) and declined those of tissue inhibitors of metalloproteinases (TIMPs). BPPs markedly ameliorated EMT in both the kidneys of UUO mice and TGF‐β1 treated HK‐2 cells. Moreover, BPP treatment decreased the expression levels of several transcriptional factors involved in regulating E‐cadherin expression, including snail, twist and ZEB1. Additionally, the Hedgehog pathway was found to be closely correlated with renal fibrosis and EMT. Altogether, our results clearly demonstrated that BPP treatment effectively inhibited the Hedgehog pathway both in renal tissues of UUO mice and TGF‐β1‐treated HK‐2 cells. Thus, BPPs ameliorated RIF and EMT in vivo and in vitro via suppressing Hedgehog signalling pathway.

Background: CASC15, one of long non-coding RNA, is involved in the regulation of many tumor biological processes, and is expected to become a new biological therapeutic target. This paper aims to elucidate the pathophysiological function of CASC15 in various tumors. Methods: The relationship between CASC15 and tumors was analyzed by searching references, and summarized the specific pathophysiological mechanism of CASC15. Results: LncRNA CASC15 is closely related to tumor development, and has been shown to be abnormally high expressed in all kinds of tumors, including breast cancer, cervical cancer, lung cancer, hepatocellular carcinoma, gastric cancer, bladder cancer, colon cancer, colorectal cancer, cardiac hypertrophy, intrahepatic cholangiocarcinoma, leukemia, melanoma, tongue squamous cell carcinoma and nasopharyngeal carcinoma. However, CASC15 has been found to be down-expressed abnormally in ovarian cancer, glioma and neuroblastoma. Besides, it is identified that CASC15 can affect the proliferation, invasion and apoptosis of tumors. Conclusion: LncRNA CASC15 has the potential to become a new therapeutic target or marker for a variety of tumors.

Background: In view of the roles of long non-coding RNA CDKN2B antisense RNA 1 (CDKN2BAS1) in various human diseases, we investigated the function of CDKN2B-AS1 and explored its therapeutic and prognostic target value in multiple biological processes. The aim of this review was to explore the molecular mechanism and clinical significance of CDKN2B-AS1 in various types of diseases. Materials and Methods: In this review, the biological functions and mechanisms of lncRNA CDKN2B-AS1 in a variety of pathophysiological processes were summarized and analyzed. The correlated studies were collected via a systematic search of PubMed, Wiley Online Library, and ScienceDirect. Results: CDKN2B-AS1 is a potential long non-coding RNA that has been shown to be aberrantly expressed in various malignancies, containing hepatocellular carcinoma, intrahepatic cholangiocarcinoma, esophageal squamous cell carcinoma, gastric cancer, colonic adenocarcinoma, cervical cancer, ovarian cancer, breast cancer, glioma, lung cancer, laryngeal squamous cell carcinoma and osteosarcoma, involving in the processes of tumor cells proliferation, migration, invasion and inhibition of tumor cells apoptosis. Besides, CDKN2B-AS1 has been proved implicated in numerous non-malignant diseases, such as idiopathic pulmonary fibrosis, endometriosis, inflammatory bowel disease, intracranial aneurysm, diabetes mellitus and its complications, primary open angle glaucoma, ischemic stroke, atherosclerosis, coronary artery diseases, hypertension and heart failure, participating in the procession of lipid, carbohydrate metabolism and inflammation regulation. Conclusions: Long non-coding RNA CDKN2B-AS1 likely serves as a promising therapeutic target or prognosis biomarker in multiple human diseases.

Ovarian cancer (OC) is ranked the first among the cancers threatening women's health. It attracts tremendous attention of cancer researchers because of its extremely high mortality rate. Recent studies have indicated that traditional herbal medicines (THMs) can play a pivotal role in cancer prevention and treatment. THMs are gaining popularity as a source of anti‐cancer agents. The plant of Balanophora polyandra, which has been used as a traditional herbal medicine, has been known for exhibiting potential haemostatic, analgesic, anti‐inflammatory and anti‐cancer properties. However, few studies on inhibitory effect of B. polyandra on OC have been performed. In the present study, we found that B. polyandra polysaccharides (BPP) induced cell cycle arrest at S phase, triggered apoptosis and inhibited migration and invasion of OC cells. Furthermore, we also found that there was a potential and close relationship between BPP and P53‐mediated pathway. Overall, these findings suggest that BPP can be a potential therapeutic agent for the treatment of OC.

Background: As a member of long non-coding RNAs (lncRNAs), maternally expressed gene 8 (MEG8) has been found involving in the progression of a variety of cancers and playing a regulatory role. Therefore, MEG8 may turn into a new therapeutic target for cancer in the future. The purpose of this review is to illustrate the molecular mechanism and physiological function of MEG8 in various cancers. Methods: We retrieved and analyzed related articles about MEG8, lncRNAs, and cancers, and then summarize the pathophysiological mechanisms of MEG8 in cancer development. Results: LncRNA MEG8 participates in various cancers progression, thus influencing the proliferation, migration, and invasion of cancers. However, the expression of MEG8 is abnormally upregulated in non-small cell lung cancer (NSCLC), pancreatic cancer (PC), liver cancer (HCC), pituitary adenoma (PA) and hemangioma (HA), and inhibited in colorectal cancer (CRC), ovarian cancer (OC) and giant cell tumor (GCT), suggesting its clinical value in cancer therapy. Conclusions: LncRNA MEG8 is expected to be a new therapeutic target or biomarker for a wide range of cancers in the future.

Background: More and more shreds of evidence show that the occurrence and development of tumors are closely related to the abnormal expression of LncRNA. A large number of experiments have found that overexpression or under-expression of MCM3AP-AS1 can affect the occurrence and development of cancer cells in varying degrees, such as proliferation, invasion, and translocation. Besides, MCM3AP-AS1 may become a promising target for many tumor biotherapies. This article reviews the pathophysiological functions and molecular mechanisms of MCM3AP-AS1 in various tumors. Methods: This paper systematically summarizes the published literatures in PubMed. The molecular mechanism of MCM3AP-AS1 in a variety of tumors is reviewed. Results: The abnormal expression of MCM3AP-AS1 in different tumors is closely related to tumor proliferation, invasion, and migration. MCM3AP-AS1 mediates or participates in related signaling pathways to regulate the expression of targeted miRNAs and proteins. MCM3AP-AS1 plays a vital role in tumor diagnosis and treatment. Conclusion: LncRNA MCM3AP-AS1 is a feasible tumor marker and a potential therapeutic target for many kinds of tumors.

Abstract: Integrins are a class of cell surface adhesion molecules composed of α subunit (ITGA) and β subunit (ITGB). They belong to heterodimer transmembrane glycoproteins. Their main function in organisms is as the receptor of cell adhesion molecules (CAMs) and extracellular matrix (ECM). According to the current research integration analysis, integrin α9 (ITGA9) is one of the integrin subunits, and there are few studies on ITGA9 among integrins. ITGA9 can improve cell migration and regulate various cellular biological functions, such as tumor cell proliferation, adhesion, invasion, and angiogenesis. However, its abnormal expression mechanism in cancer and its specific role in tumor growth and metastasis are still unknown to a great extent. This review reveals the role of ITGA9 in the complex pathogenesis of many tumors and cancers, providing a new direction for the treatment of tumors and cancers. Relevant studies were retrieved and collected through the PubMed system. After determining ITGA9 as the research object, we found a close relationship between ITGA9 and tumorigenesis by analyzing the research articles on ITGA9 in the PubMed system in the last 15 years and further determined the references mainly based on the influencing factors of the articles. Thus, the role of ITGA9 in tumor and cancer genesis, proliferation, and metastasis was reviewed and analyzed. ITGA9 is an integrin subunit, which has been proved to be abnormally expressed in many tumors. After sorting and analyzing the research data, it was found that the abnormal expression of ITGA9 in a variety of tumors, including glioblastoma, rhabdomyosarcoma, melanoma, hepatocellular carcinoma, nasopharyngeal carcinoma, multiple myeloma, non-small cell lung cancer, and prostate cancer, was closely related to the proliferation, metastasis, adhesion, and angiogenesis of tumor cells. These results suggest that ITGA9 plays an important role in the occurrence and development of tumors. The integrin subunit ITGA9 may serve as a biomarker for the diagnosis of tumors and a potential therapeutic target for anti-tumor therapies.

Mesenchymal stem cells (MSCs) are multipotent progenitors that can differentiate into multiple lineages including osteoblastic lineage. Osteogenic differentiation of MSCs is a cascade that recapitulates most, if not all, of the molecular events occurring during embryonic skeletal development, which is regulated by numerous signaling pathways including bone morphogenetic proteins (BMPs). Through a comprehensive analysis of the osteogenic activity, we previously demonstrated that BMP9 is the most potent BMP for inducing bone formation from MSCs both in vitro and in vivo. However, as one of the least studied BMPs, the essential mediators of BMP9-induced osteogenic signaling remain elusive. Here we show that BMP9-induced osteogenic signaling in MSCs requires intact Notch signaling. While the expression of Notch receptors and ligands are readily detectable in MSCs, Notch inhibitor and dominant-negative Notch1 effectively inhibit BMP9-induced osteogenic differentiation in vitro and ectopic bone formation in vivo. Genetic disruption of Notch pathway severely impairs BMP9-induced osteogenic differentiation and ectopic bone formation from MSCs. Furthermore, while BMP9-induced expression of early-responsive genes is not affected by defective Notch signaling, BMP9 upregulates the expression of Notch receptors and ligands at the intermediate stage of osteogenic differentiation. Taken together, these results demonstrate that Notch signaling may play an essential role in coordinating BMP9-induced osteogenic differentiation of MSCs., Bone morphogenetic protein (BMP) 9 is a potent inducer of osteogenic differentiation from mesenchymal stem cells, but the mediators of BMP9-induced osteogenesis remain elusive. Here, the authors show that inhibition of Notch1 signaling effectively diminishes BMP9-induced osteogenesis. Genetic disruption of Notch pathway severely impairs BMP9-induced bone formation. Thus, these results demonstrate that Notch signaling may play an essential role in coordinating osteogenic differentiation.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies with in vivo study shows that monensin blunts PDAC xenograft tumor growth by suppressing cell proliferation via targeting EGFR pathway. Therefore, our findings demonstrate that monensin can be repurposed as an effective anti-pancreatic cancer drug even though more investigations are needed to validate its safety and anticancer efficacy in pre-clinical and clinical models.

Background: Muscle blind-like-proteins (MBNL) are a class of tissue-specific RNA metabolism regulators that control pre-messenger RNA-splicing. Inactivation of MBNL can lead to myotonic dystrophy in adults. MBNL is mainly expressed in skeletal muscle, neuron tissue, thymus, liver, and kidney and plays an important role in the ultimate differentiation of muscle cells and neurons. MBNL1 is a member of the MBNL protein family. The inactivation of MBNL1 protein is particularly important in the development of myotonic dystrophy and can lead to cataract formation, abnormal muscle relaxation, cardiac and neurological dysfunction, etc. The induction of MBNL1 in tumors is known to significantly inhibit tumor progression and thus significantly prolong survival. MBNL1 antisense protein MBNL1-AS1 also plays an important role in tumor migration and development. Objective: This review reveals the role of MBNL1 and MBNL1-AS1 in the complex pathogenesis of many tumors, which provide a new target for the treatment of tumors. Methods: Correlated research are systematically retrieved via PubMed. In this review, the role of MBNL1 and MBNL1- AS1 were analyzed. Results: MBNL1 is down-regulated in breast cancer, leukemia, stomach cancer, esophageal cancer, glioma, and Huntington's disease. The function of inhibiting tumor cell metastasis decreased. It is up-regulated in cervical cancer and colorectal cancer, which can promote the development of tumor cells. Antisense protein MBNL1- AS1 can inhibit tumor cell proliferation and metastasis in colorectal cancer, non-small cell lung cancer, and gastric cancer. Conclusion: MBNL1 is an important regulator of tumor metastasis and growth, which exhibits a promising therapeutic target and can be further explored.

Background: Long non-coding RNA rhabdomyosarcoma 2-associated transcript (LncRNA RMST) can affect every aspect of tumor progressions, such as proliferation, translocation, and apoptosis. As a result, RMST can be used as an attractive biomarker for early diagnosis and clinical therapies of different disease states. This article aims to review pathophysiological functions, molecular mechanisms as well as promising biotherapies of RMST in multiple tumors. Methods: Through the systematic induction and summary of 46 papers published in PubMed concerning this study, the molecular mechanisms of RMST in all kinds of tumors have been reviewed. Results: LncRNA RMST is a tumor-related regulatory mediator, aberrantly expressed in diverse tumors, including medullary thyroid cancer, hepatocellular carcinoma, endometrial carcinoma, colon cancer, pancreatic cancer, glioma, Wilm’s tumor, and breast cancer. Furthermore, as a mechanismbased player, RMST probably guides the translation and post-translation modification, containing DNA methylation and SUMOylation. It is capable of regulating distinct tumor cells and stem cells of biological behaviors via various molecular pathways. Conclusion: LncRNA RMST, potentially as an original therapeutic target, is valuable in the occurrence, development, and apoptosis of different tumors.

Background: Long non-coding RNAs (lncRNA) have influenced numerous biology processes, which has provoked great interest. Not only that, LncRNA DUXAP8 mediates tumorigenesis by affecting the activity of miRNAs, signaling pathways, and oncogene. Methods: The functions of DUXAP8 have been summarized by reading relevant articles on PubMed. Results: lncRNA DUXAP8 acts as an oncogene in most tumors. The abnormal overexpression is associated with the proliferation, invasion, migration, and anti-autophagy of tumors. DUXAP8 exerts promotion on Akt / mTOR signaling pathway, facilitating the occurrence of tumors. Furthermore, DUXAP8 affects the activity of miRNAs and proteins, showing its significant potential as a therapeutic target in human cancers. Conclusion: LncRNA DUXAP8 has been identified as an indispensable therapeutic target of the tumors, providing clinical treatment plans.

Background: As it is known, long non-coding RNA (lncRNA) affects tumor progression, which has caused a great upsurge in recent years. It can also affect the growth, migration, and invasion of tumors. The abnormal expression of lncRNA is associated with malignant tumors. In addition, it has been proved that lncRNA is a key targeted gene for the treatment of some diseases. PART1, a member of lncRNA, has been reported as a regulator in the process of tumor occurrence and development. This study aims to reveal the biological functions, specific mechanisms, and clinical significance of PART1 in various tumor cells. Methods: Through the careful search of PUBMED, the mechanisms of the effect of PART1 on tumorigenesis and development are summarized. Results: On the one hand, the up-regulated expression of PART1 plays a tumor-promoting role in tumors, including lung cancer, prostate cancer, bladder cancer, and so on. On the other hand, PART1 is down-regulated in gastric cancer, glioma, and other tumors to play a tumor inhibitory role. In addition, PART1 regulates tumor growth mainly by targeting microRNA, such as miR-635, directly regulating the expression of proteins, such as FUS/EZH2, affecting signal pathways, such as Toll-like receptor pathway, or regulating immune cells. Conclusion: PART1 is closely related to tumors by regulating a variety of molecular mechanisms. In addition, PART1 can be used as a clinical marker for the early diagnosis of tumors and plays an important role in tumortargeted therapy.

Background: Long non-coding RNAs (lncRNA) have been identified as novel molecular regulators in cancers. LncRNA ADAMTS9-AS2 can mediate the occurrence and development of cancer through various ways, such as regulating miRNAs, activating the classical signaling pathways in cancer, and so on, which have been studied by many scholars. In this review, we summarize the molecular mechanisms of ADAMTS9-AS2 in different human cancers. Methods: Through a systematic search of PubMed, lncRNA ADAMTS9-AS2 mediated molecular mechanisms in cancer are summarized inductively. Results: ADAMTS9-AS2 aberrantly expression in different cancers is closely related to cancer proliferation, invasion, migration, and inhibition of apoptosis. The involvement of ADAMTS9-AS2 in DNA methylation, mediating PI3K / Akt / mTOR signaling pathways, and regulating miRNAs and proteins, shows its significant potential as a therapeutic cancer target. Conclusion: LncRNA ADAMTS9-AS2 can become a promising biomolecular marker and a therapeutic target for human cancer.

Background: Endometrial cancer is the fourth most common malignancy in female population worldwide. It was estimated that 65,620 new cases and 12.590 subsequent deaths occurred in 2020 in the United States. Patients with type II and advanced endometrial cancer do not respond well to the current treatments. Therefore, endometrial cancer should be better understood in order to develop more effective treatments. Objective: To provide an overview of genetic, metabolic characteristics, therapeutic strategies and current application of nanotechnology surrounding endometrial cancer. Method: Relevant articles were retrieved from Pubmed and were systematically reviewed. Results: Hypoxia inducible factor-1 and Von Hippel-Lindau factor participated in oncogenesis and progression of endometrial cancer and Nrf2 was associated with oncogenesis. Various genetic alterations were found in endometrial cancer. Examining the abnormal X chromosome inactivation may help in the diagnosis of endometrial cancer and its precancerous lesions. Some absent tumor suppressor genes, activated oncogenes were revealed by the genetically modified mouse models. Disorders in glucose and lipid metabolism were found in endometrial cancer. Current therapeutic strategies focused on the HIF-1α pathway, the mTOR pathway as well as the immunotherapy. Nanotechnology showed great potential in endometrial cancer’s early diagnosis, metastasis determination and treatment. Conclusion: Endometrial cancer has been understood in various aspects but the underlying mechanisms still remain relatively unknown, which might be the source of novel diagnostic, prognostic and therapeutic targets. Nanomedicine in endometrial cancer is poorly studied but the current researches showed great results in treating endometrial cancer. It needs further researching.

Background: Long non-coding RNA (lncRNA) breast cancer anti-estrogen resistance 4 (BCAR4) is a characterized oncogenic lncRNA in different cancers. This review is dedicated to summarize various molecular mechanisms of BCAR4 and demonstrate that the biological functions exerted by BCAR4 are good entry points for therapy. Methods: The molecular mechanism of BCAR4 acting on tumors is summarized by reviewing PubMed. Results: The expression of lncRNA BCAR4 is abnormally increased in all kinds of tumors, including colorectal cancer, prostate cancer, bladder cancer, gastric cancer, chondrosarcoma, glioma, breast cancer, glioma, gastric cancer, liver cancer, cervical cancer, lung cancer, etc. Besides, BCAR4 mediates multiple processes involved in carcinogenesis, including proliferation, invasion, anti-apoptosis, migration. Conclusion: BCAR4 may show great clinical value in this direction as a therapeutic cancer target.

Alkaloids are nitrogen-containing organic compounds widely found in natural products, which play an essential role in clinical treatment. Cellular signaling pathways in tumors are a series of enzymatic reaction pathways that convert extracellular signals into intracellular signals to produce biological effects. The ordered function of cell signaling pathways is essential for tumor cell proliferation, differentiation, and programmed death. This review describes the antitumor progression mediated by various alkaloids after inhibiting classical signaling pathways; related studies are systematically retrieved and collected through PubMed. We selected the four currently most popular pathways for discussion and introduced the molecular mechanisms mediated by alkaloids in different signaling pathways, including the NF-kB signaling pathway, PI3K/AKT signaling pathway, MAPK signaling pathway, and P53 signaling pathway. The research progress of alkaloids related to tumor signal transduction pathways and the realization of alkaloids as cancer prevention drugs by targeting signal pathways remains.

Cancer-associated bone disease is a frequent occurrence in cancer patients and is associated with pain, bone fragility, loss, and fractures. However, whether primary or non-bone metastatic gastric cancer induces bone loss remains unclear. Here, we collected clinical evidence of bone loss by analyzing serum and X-rays of 25 non-bone metastatic gastric cancer patients. In addition, C57BL mice were injected with the human gastric cancer cell line HGC27 and its effect on bone mass was analyzed by Micro-CT, immunoblotting, and immunohistochemistry. Furthermore, the degree of the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) co-cultured with HGC-27 or SGC-7901 cells was analyzed by colony-formation assay, alizarin red staining, immunofluorescence, qPCR, immunoblotting, and alkaline phosphatase activity assay. These indicated that gastric cancer could damage bone tissue before the occurrence of bone metastases. We also found that cilia formation of MSCs was increased in the presence of HGC27 cells, which was associated with abnormal activation of the Wnt/β-catenin pathway. Expression of DKK1 inhibited the Wnt/β-catenin signaling pathway and partially rescued osteogenic differentiation of MSCs. In summary, our results suggest that gastric cancer cells might cause bone damage prior to the occurrence of bone metastasis via cilia-dependent activation of the Wnt/β-catenin signaling pathway.

Background: LncRNA is a kind of non-coding RNA and its research is more popular in recent years, which has more than 200 nucleotides. It plays a significant part in various biological functions, including chromosome modification, genome modification, transcriptional activation, transcriptional interference, and other processes. FTX, at the center of the X chromosome inactivation and it has been shown that lncRNA FTX regulates cancer cells’ development, migration, and invasion in many studies. Methods: Relevant literatures were collected through PubMed system search and summarized. Results: LncRNA FTX abnormally increased in tumor cells, such as liver cancer, stomach cancer, leukemia, renal cell carcinoma, colorectal cancer, glioma, osteosarcoma, etc. However, the expression level decreased in temporal lobe epilepsy, liver cirrhosis, heart failure, etc. Conclusion: FTX may be an important regulatory factor and a potential therapeutic target in cancers.

Background: Osteoporosis (OP) is the most common bone disease, which is listed by the World Health Organization (WHO) as the third major threat to life and health among the elderly. The etiology of OP is multifactorial, and its potential regulatory mechanism remains unclear. Long non-coding RNAs (LncRNAs) are the non-coding RNAs that are over 200 bases in the chain length. Increasing evidence indicates that LncRNAs are the important regulators of osteogenic and adipogenic differentiation, and the occurrence of OP is greatly related to the dysregulation of the bone marrow mesenchymal stem cells (BMSCs) differentiation lineage. Meanwhile, LncRNAs affect the occurrence and development of OP by regulating OP-related biological processes. Methods: In the review, we summarized and analyzed the latest findings of LncRNAs in the pathogenesis, diagnosis and related biological processes of OP. Relevant studies published in the last five years were retrieved and selected from the PubMed database using the keywords of LncRNA and OP. Results/Conclusion: The present study aimed to examine the underlying mechanisms and biological roles of LncRNAs in OP, as well as osteogenic and adipogenic differentiation. Our results contributed to providing new clues for the epigenetic regulation of OP, making LncRNAs the new targets for OP therapy.

Increasing evidence has demonstrated that hypoxia was an aggressive feature in endometrial cancer (EC), which is significantly associated with the tumor grade, lymph node metastasis, and tumor resistance to chemotherapy. However, the relationship between hypoxia and the immune microenvironment in EC is not very clear. Exosomes are small membrane vesicles secreted from a variety of cell types which mediate cell-to-cell communication through transported biomolecules. Here, we investigated whether exosomes can play an immunomodulatory role in intercellular communication between EC cells and macrophages. EC KEL cells were cultured under hypoxia or normoxic condition to collect exosomes. After identification, the exosomes derived from hypoxic or normoxic KEL cells were cultured with the monocyte cell line THP-1 to study the immunoregulation function of KEL cells. The results showed that the total number of exosomes produced by hypoxic KEL cells was significantly higher than that in normoxic condition. In addition, hypoxia markedly stimulated the increase in miRNA-21 expression in the exosomes. After coculture, we found that exosomal miRNA-21 could be horizontally transferred into THP-1 cells. And then, the notably enhanced mRNA expression levels of IL-10 and CD206 in THP-1 cells were observed, suggestive of M2 polarization. To further study the effect of miRNA-21-containing exosomes, we transfected miRNA-21 mimics or inhibitor into THP-1 cells. The results showed that miRNA-21 mimics promoted IL-10 and CD206 mRNA expression levels, and the miRNA-21 inhibitor significantly prevented the alteration induced by intake of hypoxic KEL cell-derived exosomes. In summary, we found that endometrial cancer KEL cells in hypoxic condition promoted monocyte THP-1 cell transformation to M2-like polarization macrophages through delivering exosomal miRNA-21, which may be a potential mechanism of the formation of the immune microenvironment in EC progression.

Human mesenchymal stem cells (MSCs) are a heterogeneous subset of nonhematopoietic multipotent stromal stem cells and can differentiate into mesodermal lineage, such as adipocytes, osteocytes, and chondrocytes, as well as ectodermal and endodermal lineages. Human umbilical cord (UC) is one of the most promising sources of MSCs. However, the molecular and cellular characteristics of UC-derived MSCs (UC-MSCs) require extensive investigations, which are hampered by the limited lifespan and the diminished potency over passages. Here, we used the piggyBac transposon-based simian virus 40 T antigen (SV40T) immortalization system and effectively immortalized UC-MSCs, yielding the iUC-MSCs. A vast majority of the immortalized lines are positive for MSC markers but not for hematopoietic markers. The immortalization phenotype of the iUC-MSCs can be effectively reversed by flippase recombinase-induced the removal of SV40T antigen. While possessing long-term proliferation capability, the iUC-MSCs are not tumorigenic in vivo. Upon bone morphogenetic protein 9 (BMP9) stimulation, the iUC-MSC cells effectively differentiate into osteogenic, chondrogenic, and adipogenic lineages both in vitro and in vivo, which is indistinguishable from that of primary UC-MSCs, indicating that the immortalized UC-MSCs possess the characteristics similar to that of their primary counterparts and retain trilineage differentiation potential upon BMP9 stimulation. Therefore, the engineered iUC-MSCs should be a valuable alternative cell source for studying UC-MSC biology and their potential utilities in immunotherapies and regenerative medicine.

Background/Aims: As the most lethal urological cancers, renal cell carcinoma (RCC) comprises a heterogeneous group of cancer with diverse genetic and molecular alterations. There is an unmet clinical need to develop efficacious therapeutics for advanced, metastatic and/or relapsed RCC. Here, we investigate whether anthelmintic drug Niclosamide exhibits anticancer activity and synergizes with targeted therapy Sorafenib in suppressing RCC cell proliferation. Methods: Cell proliferation and migration were assessed by Crystal violet staining, WST-1 assay, cell wounding and cell cycle analysis. Gene expression was assessed by qPCR. In vivo anticancer activity was assessed in xenograft tumor model. Results: We find that Niclosamide effectively inhibits cell proliferation, cell migration and cell cycle progression, and induces apoptosis in human renal cancer cells. Mechanistically, Niclosamide inhibits the expression of C-MYC and E2F1 while inducing the expression of PTEN in RCC cells. Niclosamide is further shown to synergize with Sorafenib in suppressing RCC cell proliferation and survival. In the xenograft tumor model, Niclosamide is shown to effectively inhibit tumor growth and suppress RCC cell proliferation. Conclusions: Niclosamide may be repurposed as a potent anticancer agent, which can potentiate the anticancer activity of the other agents targeting different signaling pathways in the treatment of human RCC.

Biomedical research has advanced swiftly in recent decades, largely due to progress in biotechnology. However, this rapid spread of new, and not always-fully understood, technology has also created a lot of false or irreproducible data and artifacts, which sometimes have led to erroneous conclusions. When describing various scientific issues, scientists have developed a habit of saying "on one hand… but on the other hand…", because discrepant data and conclusions have become omnipresent. One reason for this problematic situation is that we are not always thoughtful enough in study design, and sometimes lack enough philosophical contemplation. Another major reason is that we are too rushed in introducing new technology into our research without assimilating technical details. In this essay, we provide examples in different research realms to justify our points. To help readers test their own weaknesses, we raise questions on technical details of RNA reverse transcription, polymerase chain reactions, western blotting and immunohistochemical staining, as these methods are basic and are the base for other modern biotechnologies. Hopefully, after contemplation and reflection on these questions, readers will agree that we indeed know too little about these basic techniques, especially about the artifacts they may create, and thus many conclusions drawn from the studies using those ever-more-sophisticated techniques may be even more problematic.

The heterogeneity of breast cancer makes it a challenging solid tumor to diagnose and treat. A tumor suppressor Deleted in Liver Cancer 1 (DLC1) has been reported to be down-regulated or even silenced in several kinds of cancer including breast cancer. Curcumin has been reported to modulate the growth of tumor cells through regulation of multiple cell signaling pathways and modulate epigenetic changes by CpG demethylation of many tumor suppressor genes. This study was designed to investigate the effect of curcumin on the expression of Deleted in Liver Cancer 1 (DLC1) in human breast cancer cell line MDA-MB-361 and the underlying mechanism in vitro and in vivo. Curcumin induced DLC1 expression in a dose-dependent manner. In curcumin-treated cells, methylation of DLC1 promoter was reduced and active forms of RhoA and Cdc42 were also decreased. DLC1 expression was closely related to tumor cell growth, demonstrated by Ki67 staining. Curcumin inhibited DNA methyltransferase 1 expression through down-regulation of transcription factor Sp1. Consistent with the in vitro data, in vivo administration of curcumin inhibited the growth of implanted MDA-MB-361 cells and induced DLC1 expression in tumor tissue. In MDA-MB-361 cells, curcumin down-regulates the expression of Sp1 to inhibit the expression of DNA methyltransferase 1, thus subsequently reducing hypermethylation of DLC1 promoter to induce DLC1 expression.

Background: In recent decades, the incidence of obesity has been rising globally. Obesity can often cause various inflammatory reactions, resulting in several diseases that threaten public health. The purpose of this review is to explore the role of long non-coding RNAs in metabolic obesity and find new targets for the prevention and treatment of metabolic diseases. Methods: We described the relationship between obesity and inflammation, reviewed several signaling pathways in metabolic inflammation, and summarized some of the long non-coding RNAs and their targets associated with metabolic inflammation. The related studies were retrieved through a systematic search of the PubMed database. Result: Metabolic stress during obesity can cause inflammation through several metabolic pathways. Many long non-coding RNAs can affect the progression of metabolic inflammation by affecting different pathways. Conclusion: Downregulation or antagonization of long non-coding RNAs in metabolic pathways may provide new ideas and therapeutic targets for the prevention and treatment of metabolic inflammation.

Background: Long non-coding RNAs (lncRNAs) with little or no coding capacity are associated with a plethora of cellular functions, participating in various biological processes. Cumulative study of lncRNA provides explanations to the physiological and pathological processes and new perspectives to the diagnosis, prevention, and treatment of some clinical diseases. Long non-coding RNA taurine-upregulated gene 1(TUG1) is one of the first identified lncRNAs associated with human disease, which actively involved in various physiological processes, including regulating genes at epigenetics, transcription, post-transcription, translation, and posttranslation. The aim of this review was to explore the molecular mechanism of TUG1 in various types of human diseases. Methods: In this review, we summarized and analyzed the latest findings related to the physiologic and pathophysiological processes of TUG1 in human diseases. The related studies were retrieved and selected the last six years of research articles in PubMed with lncRNA and TUG1 as keywords. Results: TUG1 is a valuable lncRNA that its dysregulated expression and regulating the biological processes were found in a variety of human diseases. TUG1 is found to exhibit aberrant expression in a variety of malignancies. Dysregulation of TUG1 has been shown to contribute to proliferation, migration, cell cycle changes, inhibited apoptosis, and drug resistance of cancer cells, which revealed an oncogenic role for this lncRNA, but some reports have shown downregulation of TUG1 in lung cancer samples compared with noncancerous samples. In addition, the molecular and biological functions of TUG1 in physiology and disease (relevant to endocrinology, metabolism, immunology, neurobiology) have also been highlighted. Finally, we discuss the limitations and tremendous diagnostic/therapeutic potential of TUG1 in cancer and other diseases. Conclusion: Long non-coding RNA-TUG1 likely served as useful disease biomarkers or therapy targets and effectively applied in different kinds of diseases, such as human cancer and cardiovascular diseases.

Background: Ovarian cancer is the most malignant tumor in gynecological tumors, with low five-year survival rate. The main reasons are diagnosis at advanced stages (the early symptoms are uncharacteristic, and most are diagnosedlate.), relapse, and resistance to existing chemotherapy drugs. Methods: Search strategy was performed in the following steps. Firstly, LncRNA related to ovarian cancer was retrieved by using the LncRNA Disease database, and articles were searched by searching keywords: ovarian cancer, drug resistance, and LncRNA retrieved from the LncRNA Disease database. Results/Conclusion: With the development of the study on drug resistance of ovarian cancer, the role of LncRNAs as sensitive biomarker and therapeutic target has emerged, providing a direction for precision medicine of ovarian cancer resistance.

The assembly and maintenance of cilia depend on intraflagellar transport (IFT) proteins, which play an important role in development and homeostasis. IFT80 is a newly defined IFT protein and partial mutation of IFT80 in humans causes diseases such as Jeune asphyxiating thoracic dystrophy (JATD) and short rib polydactyly (SRP) type III, both characterized by abnormal skeletal development. However, the role and mechanism of IFT80 in the invasion of gastric cancer is unknown. We established SGC-7901 and MKN-45 gastric cancer cell lines that stably overexpressed IFT80, as verified by quantitative reverse transcription-PCR, Western blot, and immunofluorescence. Matrix metalloproteinase-9 (MMP9) plays an important role in tumor invasion, and its expression was assessed by quantitative reverse transcription-PCR, Western blotting, and immunofluorescence. The invasion ability of IFT80 on SGC-7901 and MKN-45 cells was examined by the Matrigel invasion assay. The relationship between p75NGFR, and the p75NGFR antagonists, PD90780 and IFT80, were detected by quantitative reverse transcription-PCR and Western blotting. We first detected an IFT80 expression pattern, and found that IFT80 was highly expressed in gastric cancer clinical samples. Overexpression of IFT80 in the gastric cancer cell lines, SGC-7901 and MKN-45, led to lengthening cilia. Additionally, overexpression of IFT80 significantly improved proliferation and invasion, but inhibited apoptosis, in gastric cancer cells. We further found that overexpression of IFT80 increased p75NGFR and MMP9 mRNA and protein expression. Treatment with the p75NGFR antagonist PD90780 inhibited the increased invasion ability resulting from overexpression of IFT80 in SGC-7901 and MKN-45 gastric cancer cells. Thus, these results suggest that IFT80 plays an important role in invasion of gastric cancer through regulating the ift80/p75NGFR/MMP9 signal pathways.

MCPH1, initially identified as an hTERT repressor, has recently been implicated in mediating DNA damage response and maintaining chromosome integrity. This study is to investigate its potential role in the onset of cervical cancer. In the study, decreased expression of MCPH1 was observed in 19 of 31 cases (61.3 %) at mRNA level and 44 of 63 cases (69.8 %) at protein level of cervical tumor tissues compared with the paired nontumor tissues. Reduced MCPH1 protein expression was significantly associated with high-tumor grade (1 vs. 3 P = 0.013; 2 vs. 3 P = 0.047). In addition to inhibit SiHa cell migration and invasion, the overexpression of MCPH1 inhibited cervical cancer cells growth through inducing S phase arrest and mitochondrial apoptosis. Further analysis demonstrated cyclinA2/CDK2, CDC25C-cyclinB/CDC2, and p53/p21 pathways were involved in the MCPH1 overexpression-induced S phase arrest. Moreover, the overexpression of MCPH1 activated mitochondrial apoptosis through regulating several apoptosis-related proteins such as p53, Bcl-2, Bax, cytochrome c, caspase-3, and PARP-1. Our findings indicate that downregulated MCPH1 correlates with tumor progression in cervical cancer, and MCPH1 has an important role in regulating cell growth through regulating the cell cycle and apoptosis. Thus, it may be a crucial tumor suppressor gene and a novel candidate therapeutic target for cervical cancer.

Fangchinoline (Fan) inhibits cell proliferation and induces apoptosis in several cancer cell lines. The effects of Fan on cell growth and proliferation in breast cancer cells remain to be elucidated. Here, we show that Fan inhibited cell proliferation in the MDA-MB-231 breast cancer cell line through suppression of the AKT/Gsk- 3beta/cyclin D1 signaling pathway. Furthermore, Fan induced apoptosis by increasing the expression of Bax (relative to Bcl-2), active caspase 3 and cytochrome-c. Fan significantly inhibited cell proliferation of MDA- MB-231 cells in a concentration and time dependent manner as determined by MTT assay. Flow cytometry analysis demonstrated that Fan treatment of MDA-MB-231 cells resulted in cell cycle arrest at the G1 phase, which correlated with apparent downregulation of both mRNA and protein levels of both PCNA and cyclin D1. Further analysis demonstrated that Fan decreased the phosphorylation of AKT and GSK-3beta. In addition, Fan up-regulated active caspase3, cytochrome-c protein levels and the ratio of Bax/Bcl-2, accompanied by apoptosis. Taken together, these results suggest that Fan is a potential natural product for the treatment of breast cancer.

Lung cancer is the most common cause of cancer-related death in the world. The main types are small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC), the latter including squamous cell carcinoma (SCC), adenocarcinoma and large cell carcinoma. NSCLCs account for about 80% of all lung cancer cases. Microcephalin (MCPH1), also called BRIT1 (BRCT-repeat inhibitor of hTERT expression), plays an important role in the maintenance of genomic stability. Recently, several studies have provided evidence that the expression of MCPH1 gene is decreased in several different types of human cancers. We evaluated the expression of protein MCPH1 in 188 lung cancer and 20 normal lung tissues by immunohistochemistry. Positive MCPH1 staining was found in all normal lung samples and only some cancerous tissues. MCPH1-positive cells were significantly lower in lung carcinoma compared with normal tissues. Furthermore, we firstly found that MCPH1 expression in lung adenocarcinoma is higher than its expression in squamous cell carcinoma. Change in MCPH1 protein expression may be associated with lung tumorigenesis and may be a useful biomarker for identification of pathological types of lung cancer.

We established new methods for cloning cDNA ends that start with reverse transcription (RT) and soon proceed with the synthesis of the second cDNA strand, avoiding manipulations of fragile RNA. Our 3′-end cloning method does not involve poly-dT primers and polymerase chain reactions (PCR), is low in efficiency but high in fidelity and can clone those RNAs without a poly-A tail. We also established a cDNA protection assay to supersede RNA protection assay. The protected cDNA can be amplified, cloned and sequenced, enhancing sensitivity and fidelity. We report that RT product using gene-specific primer (GSP) cannot be gene- or strand-specific because RNA sample contains endogenous random primers (ERP). The gene-specificity may be improved by adding a linker sequence at the 5′-end of the GSP to prime RT and using the linker as a primer in the ensuing PCR. The strand-specificity may be improved by using strand-specific DNA oligos in our protection assay. The CDK4 mRNA and TSPAN31 mRNA are transcribed from the opposite DNA strands and overlap at their 3′ ends. Using this relationship as a model, we found that the overlapped sequence might serve as a primer with its antisense as the template to create a wrong-template extension in RT or PCR. We infer that two unrelated RNAs or cDNAs overlapping at the 5′- or 3′-end might create a spurious chimera in this way, and many chimeras with a homologous sequence may be such artifacts. The ERP and overlapping antisense together set complex pitfalls, which one should be aware of.

Breast cancer is the second cause of cancer-related death among Women. Current therapies for breast cancer have adverse side-effects. Selenium (Se)-containing polysaccharides have multiple health benefits to humans. Pyracantha fortuneana (P. fortuneana) contains rich Se polysaccharides. We hypothesized that Se-containing polysaccharides from P. fortuneana possess anticancer activity on breast cancer via inhibiting growth and inducing apoptosis. This study aimed to assess the anticancer effect of Se-containing polysaccharides from P. fortuneana and the underlying mechanisms. Se-containing polysaccharides were purified. Their properties and monosaccharide compositions were analyzed. Their effects on cell growth, expression of cycle proteins, apoptosis and apoptosis-related protein, and tumor growth in mouse xenograft model were examined. This extract contained 93.7% (w/w) of carbohydrate, 2.1% (w/w) of uronic acid and 3.7μg/g of Se, and was considered as Se-conjugated polysaccharides (Se-PFPs). In vitro studies showed that treatment of triple negative breast cancer (TNBC) MDA-MB-231 cells with Se-PFPs (1) inhibited cell growth dose-dependently by arresting cells at G2 phase via inhibiting CDC25C-CyclinB1/CDC2 pathway; (2) caused apoptosis associated with increased p53, Bax, Puma and Noxa, decreased Bcl2, increased Bax/Bcl2 ratio and increased activities of caspases 3/9, suggesting its effect on p53-mediated cytochrome c-caspase pathway. Treatment of nude mice bearing MDA-MB-231-derived xenograft tumors with Se-PFPs significantly reduced tumor growth without altering body weight, confirming its antitumor activity without toxic side effects. Se-PFPs enhanced doxorubicin cytotoxic effects. It is concluded that Se-containing polysaccharides from P. fortuneana potently inhibit the growth and induce apoptosis of TNBC cells and can be potential anticancer agent for TNBC.

Polysaccharides from medicinal plants exert antitumor activity in many cancers. Our previous study demonstrated that polysaccharides extracted from the selenium-enriched Pyracantha fortuneana (Se-PFPs) showed antiproliferative effect in breast cancer cell line. This study aimed to investigate the antitumor effect of Se-PFPs in ovarian cancer cells in vitro and in vivo. Se-PFPs could decrease cell viability, induce apoptosis, and inhibit migratory and invasive potentials in HEY and SKOV3 cells. These findings are supported by reduced expression of cyclin D1, Bcl-2 and MMP-9, enhanced cleavage of PARP and caspase-3, elevated activity of caspase-3 and caspase-9, and EMT (epithelial to mesenchymal transition) inhibition (elevated expression of E-cadherin and cytokeratin 19, and reduced expression of N-cadherin, vimentin, ZEB1 and ZEB2). Moreover, Se-PFPs inhibited xenografted tumor growth through inhibiting cell proliferation and inducing cell apoptosis. More importantly, Se-PFPs significantly reduced cytoplasmic β-catenin particularly nuclear β-catenin expression but increased β-catenin phosphorylation in a GSK-3β-dependent mechanism. Furthermore, β-catenin knockdown exerted similar effects on cell proliferation and invasion as seen in Se-PFPs-treated cells, while β-catenin overexpression neutralized the inhibitory effects of Se-PFPs on cell proliferation and invasion. Take together,Se-PFPs exert antitumor activity through inhibiting cell proliferation, migration, invasion and EMT, and inducing cell apoptosis. These effects are achieved by the inhibition of β-catenin signaling. Thus Se-PFPs can be used as potential therapeutic agents in the prevention and treatment of ovarian cancer.