Anti-inflammatory effects of acupuncture in the treatment of chronic obstructive pulmonary disease.

Numerous randomised controlled trials have suggested the positive effects of acupuncture on chronic obstructive pulmonary disease (COPD). However, the underlying therapeutic mechanisms of acupuncture for COPD have not been clearly summarized yet. Inflammation is central to the development of COPD. In this review, we elucidate the effects and underlying mechanisms of acupuncture from an anti-inflammatory perspective based on animal studies. Cigarette smoke combined with lipopolysaccharide is often used to establish animal models of COPD. Electroacupuncture can be an effective intervention to improve inflammation in COPD, and Feishu (BL13) and Zusanli (ST36) can be used as basic acupoints in COPD animal models. Different acupuncture types can regulate different types of inflammatory cytokines; meanwhile, different acupuncture types and acupoint options have similar effects on modulating the level of inflammatory cytokines. In particular, acupuncture exerts anti-inflammatory effects by inhibiting the release of inflammatory cells, inflammasomes and inflammatory cytokines. The main underlying mechanism through which acupuncture improves inflammation in COPD is the modulation of relevant signalling pathways: nuclear factor-κB (NF-κB) (e.g., myeloid differentiation primary response 88/NF-κB, toll-like receptor-4/NF-κB, silent information regulator transcript-1/NF-κB), mitogen-activated protein kinase signalling pathways (extracellular signal-regulated kinase 1/2, p38 and c-Jun NH2-terminal kinase), cholinergic anti-inflammatory pathway, and dopamine D2 receptor pathway. The current synthesis will be beneficial for further research on the effect of acupuncture on COPD inflammation. Please cite this article as: Jiang LH, Li PJ, Wang YQ, Jiang ML, Han XY, Bao YD, Deng XL, Wu WB, Liu XD. Anti-inflammatory effects of acupuncture in the treatment of chronic obstructive pulmonary disease. J Integr Med. 2023; 21(6): 518-527.

The role of long non-coding RNAs in drug resistance of cancer.

Long non-coding RNAs (lncRNAs), a class of long RNAs, are longer than 200 nucleotides in length but lack protein-coding capacity. LncRNAs, as critical genomic regulators, are involved in genomic imprinting regulation, histone modification and gene expression regulation as well as tumor initiation and progression. However, it is also found that lncRNAs are associated with drug resistance in several types of cancer. Drug resistance is an important reason for clinical chemotherapy failure, and the molecular mechanism of tumor resistance is complex, which is a process of multi-cause, multi-gene and multi-signal transduction pathway interaction. Then comprehending the mechanisms of chemoresistance will help find ways to control the tumor progression effectively. Therefore, in this review, we will construct lncRNAs /drug resistance interaction network and shed light on the role of lncRNAs in drug resistance.

Circular RNA circASS1 is downregulated in breast cancer cells MDA-MB-231 and suppressed invasion and migration.

AIM: The study aimed to investigate the role of circular RNA circASS1 in breast cancer cells. MATERIALS & METHODS: Circular RNAs microarray expression profile were analyzed in MCF-7, MDA-MB-231, and qRT-PCR and western blotting were used to quantify expression of circASS1 and its parental gene ASS1. Wound healing, migration and invasion assay were performed. Luciferase assay system was used to detect harbored miRNA. RESULTS: CircASS1 in MDA-MB-231 is downregulated comparing to MCF-7, and overexpression of circASS1 could suppress invasion and migration. While silence, it could promote invasion and migration. MiR-4443 functioning as a tumor promoter gene could be captured by circASS1. ASS1 is upregulated in loss-of-function experiments, while downregulated in gain-of-function experiments. CONCLUSION: CircASS1 suppresses invasion and migration capacity of breast cancer cells and harbored miR-4443.

Exosome: a novel mediator in drug resistance of cancer cells.

Exosomes are small membrane vesicles with a diameter of 40-100 nm, which are released into the intracellular environment. Exosomes could influence the genetic and epigenetic changes of receptor cells by promoting the horizontal transfer of various proteins or RNAs, especially miRNAs. Moreover, exosomes also play an important role in tumor microenvironment. Exosomes could promote the short- and long-distance exchanges of genetic information by acting as mediators of cell-to-cell communication. In addition, exosomes participate in drug resistance of tumor cells by genetic exchange between cells. It is reported that exosomes could be absorbed by recipient cells and transmit chemoresistance from drug-resistant tumor cells to sensitive ones. Then understanding the mechanisms of chemotherapy failure and controlling tumor progression effectively will be a major challenge for us. Therefore, in this review, we will briefly reveal the role of exosomes in drug resistance.

Circular RNA hsa_circ_0052112 promotes cell migration and invasion by acting as sponge for miR-125a-5p in breast cancer.

OBJECTIVES: Accumulating evidence has been reported that circular RNAs (circRNAs) are a class of relatively stable, non-coding RNAs, which are involved in the progression of many types of diseases. However, the mechanism of hsa_circ_0052112 in breast cancer cells is not entirely clear. Hsa_circ_0052112, generated from the ZNF83 gene, is selected by analyzing circRNA expression profiles of breast cancer cell by using microarray assay. In this study, we will show the role of hsa_circ_0052112 in regulating cell invasion and migration in breast cancer. METHODS: The expression level of hsa_circ_0052112 in MCF-7 and MDA-MB-231 cells was detected by RT-qPCR; we performed transwell assay to evaluate breast cancer cells' migration and invasion; predicated circRNA/miRNAs interaction using the miRanda and RNAhybrid software; identified the relationship between hsa_circ_0052112 and miR-125a-5p by luciferase activity assay and show the localization of hsa_circ_0052112 by FISH assay and show the significance of ZNF83 in clinical prognosis by Kaplan-Meier survival analysis. RESULTS: Hsa_circ_0052112 expression was significantly higher in MDA-MB-231 cells than that in MCF-7 cells. Overexpression of hsa_circ_0052112 promoted cell migration and invasion in breast cancer. Inversely, down-regulation of hsa_circ_0052112 suppressed breast cancer cells migration and invasion. Hsa_circ_0052112 was mostly located in cytoplasm. Hsa_circ_0052112 could directly sponge to miR-125a-5p; overexpression of miR-125a-5p significantly inhibited breast cancer cells migration and invasion. However, high or low expression of miR-125a-5p was not correlated with relapse free survival (RFS) by TCGA database validation, but high expression of ZNF83 was closely correlated with poor RFS by Kaplan-Meier plotter. CONCLUSIONS: These data suggest that hsa_circ_0052112 may be a potent biomarker for breast cancer, and may provide a new perspective on treatment of breast cancer.

Circular RNA hsa_circ_0072995 promotes breast cancer cell migration and invasion through sponge for miR-30c-2-3p.

AIM: To study the role of hsa_circ_0072995 in regulating the invasion and migration of breast cancer cells. MATERIALS & METHODS: Hsa_circ_0072995 expression was confirmed by quantitative real-time PCR; evaluating the migration and invasion of breast cancer cells through transwell assay; predicating circRNA/microRNAs interaction using the miRanda and RNAhybrid software; identifying the relationship between hsa_circ_0072995 and miR-30c-2-3p by luciferase activity assay; detecting the location of hsa_circ_0072995 by Fluorescence in situ hybridization assay. RESULTS: Hsa_circ_0072995 was significantly upregulated in MDA-MB-231 cells compared with MCF-7 cells. Hsa_circ_0072995 regulated the invasion and migration of breast cancer cells. Hsa_circ_0072995 existed in the nucleus and cytoplasm, and the proportion of the two was roughly equal. Hsa_circ_0072995 bound to miR-30c-2-3p. Overexpression of miR-30c-2-3p inhibited breast cancer cells migration and invasion. Low expression of miR-30c-2-3p was correlated with poor overall survival by The Cancer Genome Atlas database. CONCLUSION: Hsa_circ_0072995 may be a novel biomarker for breast cancer, and may function in metastasis of breast cancer.

MiR-30a: A Novel Biomarker and Potential Therapeutic Target for Cancer.

MicroRNAs (miRNAs) are small, highly conserved noncoding RNAs molecules, consisting of 18-25 nucleotides that regulate gene expression by binding to complementary binding sites within the 3'untranslated region (3'UTR) of target mRNAs. MiRNAs have been involved in regulating gene expression and diverse physiological and pathological processes. Several studies have reported that miR-30a, situated on chromosome 6q.13, is produced by an intronic transcriptional unit. Moreover, miR-30a has demonstrated its role in biological processes, including inhibiting proliferation and metastasis in many tumors, autophagy in chronic myelogenous leukemia, and regulating TGF-b1-induced epithelial-mesenchymal transition. However, based on the pathogenetic relationship between miR-30a and cancer in tumorigenesis, we believe that miR-30a may serve as tumor promising biomarker. Moreover, it would offer a therapeutic target for the treatment of cancer.

CircRNA: a novel type of biomarker for cancer.

Circular RNAs (circRNAs) are a class of long, non-coding RNAs molecules that shape a covalently closed continuous loop which have no 5'-3' polarity and contain no polyA tail. CircRNAs also possess relatively jarless framework and are highly tissue-specific expressed in the eukaryotic transcriptome. Emerging evidences have discovered that thousands of endogenous circRNAs are present in mammalian cells and they mediate gene expression at the transcriptional or post-transcriptional level by binding to microRNAs or other molecules and then inhibit their function. Similarly, increasing evidence indicates that circRNAs may play a role in the development of several types of diseases, including atherosclerotic vascular disease risk, neurological disorders, prion diseases, osteoarthritis and diabetes. Furthermore, circRNAs exhibit aberrant expression in multiform types of cancer, including colorectal cancer, hepatocellular carcinoma and pancreatic ductal adenocarcinoma. And based on the function of circRNAs in cancer, we believe that circRNAs may serve as diagnostic or tumor promising biomarkers. Moreover, it will provide a new therapeutic target for the treatment of cancer.

miR-30a inhibits the biological function of breast cancer cells by targeting Notch1.

miR-30a is situated on chromosome 6q.13 and is produced by an intronic transcriptional unit. However, its role in regulating the apoptosis, invasion and metastasis of breast cancer cells is not yet fully understood. The aim of this study was to research the biological function of miR­30a and its direct target gene in breast cancer. The biological function of miR­30a was determined by examining breast cancer cell growth, apoptosis, metastasis and invasion. In addition, Notch1 expression was measured by western blot analysis, and a luciferase reporter vector was constructed to identify the miR­30a target gene. miR­30a was found to be significantly downregulated in breast cancer cells. We also found that miR­30a inhibited breast cancer cell viability, migration and invasion, and induced cell apoptosis. On the whole, our data indicate that miR­30a attenuates the development of breast cancer by regulating the expression of the downstream target gene, Notch1.

The role of miR-130a in cancer.

MicroRNAs (miRs) are short and highly conserved non-coding RNAs molecules consisting of 18-25 nucleotides that regulate gene expression at post-transcriptional level by direct binding to complementary binding sites within the 3'untranslated region (3'UTR) of target mRNAs. New evidences have demonstrated that miRNAs play an important role in diverse physiological processes, including regulating cell growth, apoptosis, metastasis, drug resistance, and invasion. In chromosomes 11 and 22 of the miR-130 family, paralogous miRNA sequences, miR-130a and miR-130b are situated, respectively. MiR-130a has participated in different pathogenesis, including hepatocellular carcinoma, cervical cancer, ovarian cancer, glioblastoma, prostate carcinoma, leukemia, etc. Most important of all, more and more evidences indicate that miR-130a is associated with drug resistance and acts as an intermediate in PI3 K/Akt/PTEN/mTOR, Wnt/ß-catenin and NF-kB/PTEN drug resistance signaling pathways. Drug resistance has emerged as a major obstacle to successful treatment of cancer nowadays and in this review, we will reveal the function of miR-130a in cancer, especially in drug resistance. Therefore, it will provide a new therapeutic target for the treatment of cancer, especially in chemotherapy.

AMD3100 Attenuates Matrix Metalloprotease-3 and -9 Expressions and Prevents Cartilage Degradation in a Monosodium Iodo-Acetate-Induced Rat Model of Temporomandibular Osteoarthritis.

PURPOSE: Temporomandibular joint osteoarthritis (TMJOA) is an important subtype of temporomandibular disorder. This study investigated the inflammatory role of the stromal cell-derived factor-1 (SDF-1) and C-X-C chemokine receptor-4 (CXCR4) axis and the probable signaling pathway involved in matrix metalloprotease (MMP)-3 and MMP-9 productions stimulated by the SDF-1-CXCR4 axis in an experimental rat model of TMJOA. MATERIALS AND METHODS: Rats were randomly divided into a control group, a pathologic model group, and an AMD3100 group. Effects of the bicyclam derivative AMD3100 (the specific antagonist of SDF-1-CXCR4 axis) were studied in TMJOA experimentally induced by monosodium iodo-acetate. Productions of SDF-1 and CXCR4 were compared in the normal and pathologic model groups, and cartilage changes and expressions of MMP-3, MMP-9, and phosphorylated extracellular signal-regulated kinase (p-ERK) were compared in the control, pathologic model, and AMD3100 groups. RESULTS: Expressions of SDF-1 and CXCR4 in the pathologic model group were increased compared with the control group (P < .05). Releases of MMP-3, MMP-9, and p-ERK and cartilage changes were downregulated in the AMD3100 group compared with the pathologic model group (P < .05), and these changes occurred in a dose-dependent manner with AMD3100 concentrations. Moreover, there were strong predictive relations between the expression of p-ERK with MMP-3 (r(2) = 0.419; P < .001) and with MMP-9 (r(2) = 0.542; P < .001). CONCLUSIONS: The SDF-1-CXCR4 signaling pathway plays a proinflammatory role in experimental TMJOA, the bicyclam derivative AMD3100 can alleviate the severity of experimental TMJOA, and there might be a potential relation between the SDF-1-CXCR4 axis and the ERK signaling pathway.

MiR-139-5p inhibits the biological function of breast cancer cells by targeting Notch1 and mediates chemosensitivity to docetaxel.

OBJECTIVES: MiRNA-139 is located at 11q13.4 and it has anti-oncogenic and antimetastatic activity in humans. However, its role in controlling apoptosis, invasion and metastasis and the development of chemosensitivity to docetaxel in breast cancer cells are not fully understood. The aim of this study was to research the biological function of miR-139-5p and the efficacy of chemosensitivity to docetaxel. METHODS: MiR-139-5p expression in MCF-7, MCF-7/Doc cells and in selected breast cancer tissue samples was confirmed by real-time PCR; cell viability was analyzed by Cell Counting Kit-8 assay; apoptosis and cell cycle were analyzed by flow cytometry; control of metastasis and invasion of breast cancer cells was measured by transwell assay; expression of Notch1 was measured by western blot; a luciferase reporter vector was constructed to identify the miR-139-5p target gene. RESULTS: MiR-139-5p was significantly down-regulated in breast cancer cells. MiR-139-5p inhibits the viability of breast cancer cells. MiR-139-5p induces apoptosis, causes cell cycle arrest in S phase, inhibits migration and invasion in breast cancer cells, however, MiR-139-5p play the opposite role in docetaxel-induced breast cancer cells. CONCLUSIONS: MiR-139-5p not only attenuated the development of breast cancer cells but also mediated drug-resistance by regulating the expression of the downstream target gene Notch1.

MiR-139-5p: promising biomarker for cancer.

MicroRNAs (miRNAs) were reported to be associated with cancer progression and carcinogenesis. MiRNAs are small, highly conserved, small non-coding RNA molecules, consisting of 18-25 nucleotides that control gene expression at the post-transcription level. By binding to complementary binding sites within the 3' untranslated region (3'UTR) of target messenger RNAs (mRNAs), inhibiting translation or promoting degradation of mRNAs. MicroRNAs not only play an important part in regulating gene expression but also controlling diverse physiological and pathological processes. Similarly, several studies have demonstrated that miRNAs have been involved in regulating various biological processes, including apoptosis, proliferation, cellular differentiation, metabolism, signal transduction, and carcinogenesis. MiRNA-139, which is located in 11q13.4 and has anti-oncogenic and antimetastatic activity in humans, meanwhile, was identified to be downregulated in previous studies. However, based on the pathogenetic relationship between cancer and the role of miR-139-5p in tumorigenesis, we consider that miR-139-5p may be the candidates to serve as promising biomarkers with sufficient sensitivity and specificity for the diagnosis of cancer in a clinical setting; moreover, it would offer a new safe and effective way in further molecular targeting cancer treatment, as well as improving overall survival of patients.