MiR-142-3p Overexpression Increases Chemo-Sensitivity of NSCLC by Inhibiting HMGB1-Mediated Autophagy

Background/Aims: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has the third highest mortality rate among all cancers. MicroRNAs are a class of endogenous, single-stranded short noncoding RNAs. The purpose of this study was to study the role of microRNA-873 in HCC. Methods: The expression of miRNA-873 and tumor suppressor in lung cancer 1 (TSLC1) in HCC tissues and cell lines was detected by real-time quantitative RT-PCR (RT-qPCR) or western blot. A CCK-8 assay was used to examine cell proliferation; flow cytometry was used to assess the cell cycle; the Transwell migration assay was used to test for metastasis. Luciferase assays were performed to assess whether TSLC1 was a novel target of miRNA-873. Results: We showed that miRNA-873 was upregulated in HCC tissues and cell lines compared with the normal control. Knockdown of miRNA-873 inhibited the growth and metastasis of HepG2 and accelerated G1 phase arrest, while overexpression of miRNA-873 had the opposite effect. The dual-luciferase reporter assays revealed that TSLC1 was a novel target of miRNA-873. Further study showed that TSLC1 was decreased in HCC tissues and cell lines. There was a negative correlation between the expression levels of TSLC1 and miRNA-873. The effect of miRNA-873 overexpression was neutralized by TSLC1. We also found that miRNA-873 activated the PI3K/AKT/mTOR signaling pathway and promoted HCC. Conclusions: Our data demonstrated that miRNA-873 promoted HCC progression by targeting TSLC1 and provided a new target for the therapy of HCC.

Section: Discussionmentioning

confidence: 99%

MicroRNA-873 Promotes Cell Proliferation, Migration, and Invasion by Directly Targeting TSLC1 in Hepatocellular Carcinoma

Han¹,

Zhang²,

Ni³

et al. 2018

“…Most recent, miR-142-3p has been reported to be associated with several types of cancer. MiR-142-3p was significantly upregulated in renal cell carcinoma and miR-142-3p inhibitor could significantly suppressed cell migration and proliferation, and promoted cell apoptosis in 786-O and ACHN cells [30]; miR-142-3p was down-regulated in both cancer cell lines and cancer specimens and miR-142-3p overexpression suppressed proliferation by leading cell cycle arrest in G2/M [31]; miR-142-3p was downregulated in hepatocellular carcinoma (HCC) tissues and the overexpression of miR-142-3p inhibited aerobic glycolysis and thus proliferation of HCC cells by targeting lactate dehydrogenase A (LDHA) [32]; miR-142-3p was significantly lower in ovarian cancer tissues and cell lines and Ectopic expression of miR-142-3p significantly inhibited the proliferation of ovarian cancer cells by targeting sirtuin 1 (SIRT1) and increased the sensitivity of SKOV3/DDP cells to cisplatin [33]; miR-142-3p was markedly downregulated in gastric cancer tissues and could inhibit the proliferation, invasion and migration of gastric cancer cells [34]; miR-142-3p inhibited proliferation and invasion in HeLa and SiHa cells by targeting frizzled 7 receptor [FZD7] [35]; miR-142-3p miR-142-3p downregulated MGMT expression and also sensitizedGlioblastoma multiforme [GBM] cells to alkylating drugs [36]; miR-142-3p overexpression increased PI3K, Akt, and mTOR phosphorylation by targeting High mobility group box-1 [HMGB1] in NSCLS cells [37]. According to CRC, three studies have suggested that miR-142-3p is involved in CRC development.…”

Section: Discussionmentioning

confidence: 99%

miR-142-3p Suppresses Cell Growth by Targeting CDK4 in Colorectal Cancer

Zhu

Yang

et al. 2018

Background/Aims: Deregulation of microRNAs (miRNAs) has been associated with a variety of cancers, including colorectal cancer (CRC). Here, we investigated anomalous miR-142-3p expression and its possible functional consequences in primary CRC samples. Methods: The expression of miR-142-3p was measured by quantitative RT-PCR in 116 primary CRC tissues and adjacent non-tumor tissues. The effect of miR-142-3p up- or down-regulation in CRC-derived cells was evaluated in vitro by cell viability and colony formation assays and in vivo by growth assays in xenografted nude mice. Results: Using quantitative RT-PCR, we found that miR-142-3p was down-regulated in 78.4 % (91/116) of the primary CRC tissues tested when compared to the adjacent non-tumor tissues. We also found that the miR-142-3p mimic reduced in vitro cell viability and colony formation by inducing cell cycle arrest in CRC-derived cells, and inhibited in vivo tumor cell growth in xenografted nude mice. Inversely, we found that the miR-142-3p inhibitor increased the viability and colony forming capacity of CRC-derived cells and tumor cell growth in xenografted nude mice. In addition, we identified CDK4 as a potential target of miR-142-3p by predictions and dual-luciferase reporter assays. Concordantly, we found that miR-142-3p mimics and inhibitors could decrease and increase CDK4 protein levels in CRC-derived cells, respectively. Conclusion: From our results we conclude that miR-142-3p may act as a tumor suppressor in CRC and may serve as a tool for miRNA-based CRC therapy.

“…The regulatory role of miR-142-3p has been reported in several types of cancer. For example, miR-142-3p overexpression increases the chemosensitivity of non-small cell lung cancer (NSCLC) by inhibiting high-mobility group box 1-mediated autophagy Chen et al [14]. In addition, it can modulate osteosarcoma progression by interacting with metastasisassociated lung adenocarcinoma transcript-1 Liu et al [15].…”

Section: Introductionmentioning

confidence: 99%

lncRNA TUG1-Mediated Mir-142-3p Downregulation Contributes to Metastasis and the Epithelial-to-Mesenchymal Transition of Hepatocellular Carcinoma by Targeting ZEB1

Liu

Jin

et al. 2018

Background/Aims: MicroRNA-142-3p (miR-142-3p) is dysregulated in many malignancies and may function as a tumor suppressor or oncogene in tumorigenesis and tumor development. However, few studies have investigated the clinical significance and biological function of miR-142-3p in hepatocellular carcinoma (HCC). Methods: The expression levels of taurine upregulated gene 1 (TUG1), miR-142-3p, and zinc finger E-box-binding homeobox 1 (ZEB1) were evaluated in HCC tissues and cell lines by quantitative real-time PCR. MTT and colony formation assays were used to detect cell proliferation ability, transwell assays were used to assess cell migration and invasion, and luciferase reporter assays were used to examine the interaction between the long noncoding RNA TUG1 and miR-142-3p. Tumor formation was evaluated through in vivo experiments. Results: miR-142-3p was significantly downregulated in HCC tissues, but TUG1 was upregulated in HCC tissues. Knockdown of TUG1 and upregulation of miR-142-3p inhibited cell proliferation, cell migration, cell invasion, and the epithelial-mesenchymal transition (EMT). miR-142-3p was found to be a prognostic factor of HCC, and the mechanism by which TUG1 upregulated ZEB1 was via direct binding to miR-142-3p. In vivo assays showed that TUG1 knockdown suppressed cell proliferation and the EMT in nude mice. Conclusion: The results of this study suggest that the TUG1/miR-142-3p/ ZEB1 axis contributes to the formation of malignant behaviors in HCC.