Fang Wang

Lung cancer is an significant cause of death worldwide, and non–small‐cell lung cancer (NSCLC) is the most common type of lung cancer. MicroRNAs (miRNAs) have been identified to play key roles in NSCLC development. Recently, it has been reported that miR‐605‐5p is a cancer‐related miRNA in several types of tumors. In this study, we study the role of miR‐605‐5p in NSCLC cells. We find that miR‐605‐5p is upregulated in NSCLC cells. Overexpression of miR‐605‐5p significantly promotes lung cancer invasion and migration in H460 and H1299 cells. Besides this, miR‐605‐5p also promotes lung cancer cell carcinoma proliferation and metastasis in vivo. However, downregulation of miR‐605‐5p inhibits cell invasion and migration by inhibiting lung cancer cell carcinoma proliferation and metastasis. In addition, the luciferase report assay identifies 3′‐untranslated region tumor necrosis factor α‐induced protein 3 (TNFAIP3) as a target of miR‐605‐5p. Silencing of TNFAIP3 promotes invasion and proliferation in lung cancer. In addition, the knockdown of TNFAIP3 restores the significant decrease in invasion and proliferation in miR‐605‐5p‐inhibitor–transfected lung cancer cells. In conclusion, miR‐605‐5p promotes invasion and proliferation by targeting TNFAIP3 in NSCLC, and may provide possible biomarkers for NSCLC therapy.

Malignant glioma remains the most frequent form of primary brain tumors all over the world. The gliomagenesis is characterized by various molecular processes such as neoplastic transformation, dysregulation of the cell cycle, and angiogenesis. Among these biomolecular events, the existence of inflammation and oxidative stress pathways in the development of glioma has been reported. PTPN2 is associated with several inflammatory disorders. However, the biological role of PTPN2 in inflammation responses and oxidative stress pathways involved in glioma remains poorly known. Here, we focused on its function in glioma development. Here, we observed that PTPN2 was significantly increased in glioma especially in a grade‐dependent manner. Meanwhile, interferon‐γ and tumor necrosis factor‐α, which have been identified as crucial inflammation cytokines, were able to trigger PTPN2 expression in a dose‐dependent course in T98G cells. Then, we found that PTPN2 was oxidated and inactivated by H₂O₂. Meanwhile, H₂O₂ induced glioma cell colony formation capacity and increased ki‐67 expression confirmed by flow cytometry assay. Finally, T98G cells were transfected with PTPN2 shRNA and it was shown that knockdown of PTPN2 obviously inhibited T98G cell colony formation and induced cell apoptosis. In summary, our findings indicated that PTPN2 could be induced by inflammatory response and oxidative stress and its deficiency depressed glioma cell growth.

MicroRNAs (miRNA) play important roles in neuroinflammation and neuropathic pain development; however, the underlying mechanism requires further investigation. The expression of miR‐21‐5p was remarkably upregulated in chronic constrictive injury (CCI) rat model. A significant alleviated neuropathic pain development and reduced the expression of cytokines was observed in CCI rat after exogenous injection of miR‐21‐5p mimic. The dual‐luciferase analysis revealed that tissue inhibitor of metalloproteinase‐3 (TIMP3) and chemokines C‐C motif ligand 1 (CCL1) was direct downstream target of miR‐21‐5p. Moreover, silencing of TIMP3 and CCL1 could rescue mechanical allodynia, thermal hyperalgesia and cytokine release in CCI rat, suggesting that TIMP3 and CCL1 exert their function by mediating neuroinflammation in neuropathic pain development. Therefore, we have identified a novel miR‐21‐5p–CCL1/TIMP3‐cytokine axis in regulation of neuropathic pain development in CCI rat model, which is valuable for enhancing our understanding of neuropathic pain and developing miRNAs as potential therapeutic options in the future.

Neuropathic pain has been reported as a type of chronic pain due to the primary dysfunction of the somatosensory nervous system. It is the most serious types of chronic pain, which can lead to a significant public health burden. But, the understanding of the cellular and molecular pathogenesis of neuropathic pain is barely complete. Long noncoding RNAs (lncRNAs) have recently been regarded as modulators of neuronal functions. Growing studies have indicated lncRNAs can exert crucial roles in the development of neuropathic pain. Therefore, our present study focused on the potential role of the lncRNA Colorectal Neoplasia Differentially Expressed (CRNDE) in neuropathic pain progression. Firstly, a chronic constrictive injury (CCI) rat model was built. CRNDE was obviously increased in CCI rats. Interestingly, overexpression of CRNDE enhanced neuropathic pain behaviors. Neuroinflammation was induced by CRNDE and as demonstrated, interleukin‐10 (IL‐10), IL‐1, IL‐6, and tumor necrosis factor‐α (TNF‐α) protein levels in CCI rats were activated by LV‐CRNDE. For another, miR‐136 was obviously reduced in CCI rats. Previously, it is indicated that miR‐136 participates in the spinal cord injury via an inflammation in a rat model. Here, firstly, we verified miR‐136 could serve as CRNDE target. Loss of miR‐136 triggered neuropathic pain remarkably via the neuroinflammation activation. Additionally, IL6R was indicated as a target of miR‐136 and miR‐136 regulated its expression. Subsequently, we confirmed that CRNDE could induce interleukin 6 receptor (IL6R) expression positively. Overall, it was implied that CRNDE promoted neuropathic pain progression via modulating miR‐136/IL6R axis in CCI rat models.

Long noncoding RNAs (lncRNAs) are involved in multiple nervous system diseases, including neuropathic pain. Previous studies have demonstrated that lncRNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) has been identified as a diagnostic biomarker in many diseases. Nevertheless, the function of MALAT1 in neuropathic pain progression is still unclear. Here, we established a chronic constriction injury (CCI) rat model. We found that MALAT1 was remarkably upregulated in CCI rats. In addition, neuropathic pain behaviors such as mechanical and thermal hyperalgesia were reduced by the inhibition of MALAT1. Meanwhile, the loss of MALAT1 was able to depress the neuroinflammation process via the inhibition of COX‐2, interleukin‐1β, and interleukin‐6. A previous study has indicated that miR‐206 upregulation can restrain the CCI‐induced neuropathic pain. Furthermore, we exhibited that miR‐206 was significantly downregulated and silence of MALAT1 restrained its expression in CCI rats. For another, ZEB2 was a target of miR‐206 and it was shown that ZEB2 was elevated in CCI rats in a time‐dependent manner. Overexpression of miR‐206 obviously suppressed ZEB2 levels in rat microglial cells. Subsequently, it was demonstrated that upregulation of miR‐206 rescued the neuropathic pain triggered by ZEB2 overexpression in vivo through neuroinflammation inhibition. Overall, we indicated that suppression of MALAT1 ameliorated neuropathic pain progression via miR‐206/ZEB2 axis.

MicroRNA (miRNA) are significant regulators of neuropathic pain development and neuroinflammation can contribute a lot to the progression of neuropathic pain. Recently, miR‐98 has been reported to be involved in various diseases. However, little is known about the role of miR‐98 in neuropathic pain development and neuroinflammation. Therefore, our study was aimed to investigate the function of miR‐98 in neuropathic pain via establishing a rat model using chronic constriction injury (CCI) of the sciatic nerve. Here, we observed that miR‐98 was downregulated in CCI rat models. Overexpression of miR‐9 was able to inhibit neuropathic pain progression. Recently, STAT3 has been reported to serve a key role in various processes, including inflammation. Interestingly, our study indicated that STAT3 was dramatically upregulated and activated in CCI rats. By using informatics analysis, STAT3 was predicted as a direct target of miR‐98 and the direct correlation was confirmed. Then, miR‐98 was overexpressed in CCI rats and it was found that miR‐98 was able to repress neuropathic pain development via inhibiting the neuroinflammation. As displayed, interleukin 6 (IL‐6), IL‐1β, and tumor necrosis factor‐α (TNF‐α) expression was obviously induced in CCI rats, while miR‐98 reduced their protein levels. Finally, we found that overexpression of STAT3 reversed the inhibitory effect of miR‐98 on neuropathic pain development. Taken these together, we reported that overexpression of miR‐98 attenuated neuropathic pain development via targeting STAT3 in CCI rat models.

To study the roles of STARD13 in cellular apoptosis of hepatocellular carcinoma (HCC). Quantitative real-time PCR and immunohistochemistry analyses showed that the expression levels of STARD13 and Fas were lower in clinical HCC tissues than in normal tissues and were positively correlated, which is consistent with the results analyzed by The Cancer Genome Atlas (TCGA) data. Patients with higher STARD13 or Fas expression levels had longer overall survival. Additionally, STARD13 3′-UTR enhanced cellular apoptosis and the 3′-UTRs of STARD13 and Fas were predicted to harbor nine similar miRNA binding sites. And STARD13 3′-UTR promoted Fas expression in a 3′-UTR- and miRNA-dependent way and increased the sensitivity of HCC cells to chemotherapy. Importantly, the coding sequence of STARD13 did not increase Fas expression. STARD13 3′-UTR promotes HCC apoptosis through acting as a ceRNA for Fas.