MicroRNA-367 Inhibits Breast Cancer and Promotes Apoptosis by Targeting AT-Rich Interactive Domain-Containing Protein 1B

Introduction: Breast cancer (BC) developed in the glandular epithelial tissue of breast. microRNA (miR)-367 is an important player in cancer progression, but has never been studied in BC. This experiment tries to probe the mechanism of miR-367 in BC treatment with downstream target gene. Materials and Methods: Human BC cell lines and healthy breast epithelium cells were applied in this study. After the transfection of miR-367 inhibitor or mimic into BC cells, functional assays were conducted to measure cell growth. Afterwards, flow cytometry was employed in apoptosis verification. Then, target relation between miR-367 and ARID1B was certified. Furthermore, ARID1B level was also measured. Results: miR-367 was underexpressed in human BC cells (p < 0.05). Besides, overexpressed miR-367 inhibited BC cell proliferation and encouraged apoptosis, while underexpressed miR-367 led to an opposite outcome (p < 0.05). This experiment then implied that miR-367 dramatically suppressed the activity of cell transfected with ARID1B-wild type. miR-367 overexpression quenched ARID1B level in BC cells; while silencing miR-367 upregulated ARID1B expression (p < 0.05). Conclusion: Our experiment discovered that miR-367 quenched BC cell growth and promoted apoptosis by targeting ARID1B. This investigation may provide novel insights in BC treatment.

LncRNA Neu Mediates Bone Marrow Mesenchymal Stem Cells (BMSCs) Growth and Promotes Cervical Cancer Progression Through Suppression of MicroRNA-625

The tumorigenesis mechanism of cervical cancer (CC) is complicated as several pathways deserve exploration. LncRNAs are recently highlighted to be involved in various biological processes. The role of bone marrow mesenchymal stem cells (BMSCs) in tumor regulation is recently investigated. Herein, we aimed to explore the interaction between lncRNA Neu and microRNA (miR)-625 and BMSCs in CC. Expression levels of lncRNA Neu and miR-625 in CC cells and BMSCs were determined by RT-qPCR. The relationship between lncRNA Neu and miR-625 was analyzed by Pearson correlation analysis. After cancer cells were transfected with siRNA-Neu, CCK-8 assay and clone formation assay were conducted to determine cell proliferation and viability. LncRNA Neu was highly expressed in CC cells and poorly expressed in BMSCs. Knockdown of lncRNA Neu attenuated cell viability and proliferation while increased miR-625 expression. MiR-625 expression was negatively correlated with expression of lncRNA Neu in CC cells. Overexpression of miR-625 resulted in weakened CC cell viability. Collectively, lncRNA Neu was highly expressed in CC and promoted the development of CC through stimulating the growth of BMSCs and suppressing miR-625 expression. These findings provide a novel insight into targeted therapy for CC.

miR-29b Derived from Bone Marrow Stromal Cell (BMSC) Exosomes Improves Laryngeal Carcinoma by Inhibiting Forkhead Box Protein P1 (FOXP1) to Decrease Cyclin E2 Transcription

This study intends to investigate whether miR-29b derived from BMSC exosomes (BMSC-exos) affects laryngeal cancer progression. RT-qPCR detected miR-29b level in BMSCs and BMSC-exos. After miR-29b was overexpressed in BMSCs, exos were extracted from BMSCs and used to treat laryngeal cancer cells, followed by CCK-8 assay and soft agar assay. When cells were treated with FOXP1 inhibitor or cyclin E2 vector, Western blot analyzed the expression of related proteins and flow cytometry assessed cell cycle distribution. In vivo experiment was conducted to assess miR-29b’s effect on tumor growth. miR-29b was upregulated in BMSC-exos, but lowly expressed in cancer cells. miR-29b upregulation inhibited the proliferation of laryngeal cancer cells and delayed tumor progression In vivo by inducing cell cycle arrest. Importantly, miR-29b bound 3′UTR of FXOP1 to inhibit its expression, and further reduced cyclin E2 level. sh-FXOP1 or cyclin E2 vector can restore the cell cycle and proliferation caused by miR-29b. In conclusion, miR-29b enriched in BMSC-exo can down-regulate cyclin E2 expression through targeted inhibition of FXOP1, thereby inhibiting the progression of laryngeal cancer.

The Role of miR-4256/HOXC8 Signaling Axis in the Gastric Cancer Progression: Evidence From lncRNA-miRNA-mRNA Network Analysis

Gastric cancer is a deadly human malignancy and the molecular mechanisms underlying gastric cancer pathophysiology are very complicated. Thus, further investigations are warranted to decipher the underlying molecular mechanisms. With the development of high-throughput screening and bioinformatics, gene expression profiles with large scale have been performed in gastric cancer. In the present study, we mined The Cancer Genome Atlas (TCGA) database and analyzed the gene expression profiles between gastric cancer tissues and normal gastric tissues. A series of differentially expressed lncRNAs, miRNAs and mRNAs between gastric cancer tissues and normal gastric tissues were identified. Based on the differentially expressed genes, we constructed miRNA-mRNA network, lncRNA-mRNA network and transcriptional factors-mRNA-miRNA-lncRNA network. Furthermore, the Kaplan survival analysis showed that high expression levels of EVX1, GBX2, GCM1, HOXC8, HOXC9, HOXC10, HOXC11, HOXC12 and HOXC13 were all significantly correlated with shorter overall survival of the patients with gastric cancer. On the other hand, low expression level of HOXA13 was associated with shorter overall survival of patients with gastric cancer. Among these hub genes, we performed the in vitro functional studies of HOXC8 in the gastric cancer cells. Knockdown of HOXC8 and overexpression of miR-4256 both significantly repressed the gastric cancer cell proliferation and migration, and miR-4256 repressed the expression of HOXC8 via targeting its 3’ untranslated region in gastric cancer cells. Collectively, our results revealed that a complex interaction networks of differentially expressed genes in gastric cancer, and further functional studies indicated that miR-4256/HOXC8 may be an important axis in regulating gastric cancer progression.

Inhibitory Effect of Etravirine, a Non-Nucleoside Reverse Transcriptase Inhibitor, via Anterior Gradient Protein 2 Homolog Degradation against Ovarian Cancer Metastasis

Anterior gradient protein 2 homolog (AGR2), an endoplasmic reticulum protein, is secreted in the tumor microenvironment. AGR2 is a member of the disulfide isomerase family, is highly expressed in multiple cancers, and promotes cancer metastasis. In this study, we found that etravirine, which is a non-nucleoside reverse transcriptase inhibitor, could induce AGR2 degradation via autophagy. Moreover, etravirine diminished proliferation, migration, and invasion in vitro. Moreover, in an orthotopic xenograft mouse model, the combination of etravirine and paclitaxel significantly suppressed cancer progression and metastasis. This drug may be a promising therapeutic agent for the treatment of ovarian cancer.