microRNA-134 inhibits melanoma growth and metastasis by negatively regulating collagen triple helix repeat containing-1 (CTHRC1).
Melanoma, a malignant tumor of melanocytes, is considered to be the most aggressive of skin cancers and its incidence keeps increasing worldwide. miR-134 and CTHRC1 have been demonstrated to be involved in the occurrence and development of various tumors. However, their roles are still elusive in the progression of melanoma. qRT-PCR and western blot (WB) were used to examine the expressions of miR-134 and CTHRC1 in clinical specimens of melanoma patients and melanoma cell lines. Dual-luciferase reporter assay was applied to verify the target interaction between miR-134 and CTHRC1. The mRNA and protein expressions of CTHRC1 were measured by qRT-PCR and WB after treatment by miR-134 inhibitor and mimic. Subsequently, CCK8, colony formation assay, and flow cytometry were utilized to assess the influences of miR-134 and CTHRC1 on cell growth of melanoma. Cell migration and invasion experiments were performed to evaluate the effects of miR-134 and CTHRC1 on metastasis of melanoma. It was shown that CTHRC1 was up-regulated and miR-134 was down-regulated in melanoma patients and cell lines. CTHRC1 was demonstrated to be a direct target of miR-134. Ultimately, we also found that up-regulated miR-134 expression and down-regulated CTHRC1 expression could suppress cell proliferation and cell colony formation, promote apoptosis, delay the cell cycle, and hinder cell migration and invasion. Our findings suggest that miR-134 could inhibit the growth and metastasis of melanoma by negatively regulating CTHRC1.
Li Y
，Fu Y
，Gao Y
，Li H
，Ma L
，Shu C
，Li N
，Ma C
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PEX5, a novel target of microRNA-31-5p, increases radioresistance in hepatocellular carcinoma by activating Wnt/β-catenin signaling and homologous recombination.
Rationale: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, with high recurrence and metastasis rates. Although radiation is an effective treatment for tumors, it is often limited by intrinsic radioresistance in HCC. The contributions of dysregulated microRNAs, including miR-31-5p, to HCC progression have been recently reported. However, the role of miR-31-5p in the radiation response of HCC is unknown. In this study, we aimed to investigate the impact of miR-31-5p on HCC radiosensitivity. Methods: miR-31-5p expression in HCC tissues, paired adjacent tissues, and HCC cell lines was measured using quantitative real-time polymerase chain reaction and in situ hybridization. Bioinformatic analyses, gain- and loss-of-function experiments, and luciferase reporter assays were performed to validate peroxisomal biogenesis factor 5 (PEX5) as a direct target of miR-31-5p. The biofunctions of PEX5 and miR-31-5p in HCC were determined by Transwell, wound-healing, and Cell Counting Kit-8 (CCK8) assays. A colony formation assay was used to evaluate the radiosensitivity of HCC cells. The interaction among PEX5, β-catenin, Rac1, and JNK-2 was confirmed by coimmunoprecipitation. A xenograft tumor model was established to validate the effects of miR-31-5p and PEX5 on HCC progression and radiosensitivity in vivo.Results: Low expression of miR-31-5p in HCC specimens, as observed in this study, predicted a poor clinical outcome. However, the expression pattern of PEX5, as a direct target of miR-31-5p, was opposite that of miR-31-5p, and high PEX5 expression indicated poor prognosis in HCC patients. Ectopic expression of PEX5 increased the proliferation, migration, and invasion abilities and enhanced the radioresistance of HCC cells in vitro and in vivo; however, these phenotypes were inhibited by miR-31-5p. Mechanistically, PEX5 stabilized cytoplasmic β-catenin and facilitated β-catenin nuclear translocation to activate Wnt/β-catenin signaling. Moreover, upon radiation exposure, PEX5 reduced excessive reactive oxygen species (ROS) accumulation and activated the homologous recombination (HR) pathway, which protected HCC cells from radiation-induced damage. Conclusions: Our findings demonstrated a novel role for PEX5 as a miR-31-5p target and a mediator of the Wnt/β-catenin signaling and HR pathways, providing new insights into studying HCC radiation responses and implicating PEX5 and miR-31-5p as potential therapeutic targets in HCC.
Wen J
，Xiong K
，Aili A
，Wang H
，Zhu Y
，Yu Z
，Yao X
，Jiang P
，Xue L
，Wang J
... -
《Theranostics》
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