Li Zhang

Breast cancer is a disease in which cancer cells form in the tissues of the breast. The present study aimed to explore the effect of the flavonoid compound quercetin on the growth and apoptosis of human breast cancer cells. Varying concentrations (12.5, 25, 50, 100, 200 µM) of quercetin were applied to cultured MCF-7 human breast cancer cells for defined lengths of time. At 50 to 200 µM doses, quercetin significantly inhibited the proliferation of MCF-7 cells assessed by MTT colorimetry, in both dose- and time-dependent manners (P<0.05). The compound also increased apoptosis after 48 h of exposure (P<0.05). Furthermore, following quercetin treatment Bcl-2 expression decreased significantly while Bax expression increased significantly (P<0.05). In brief, quercetin inhibits cell growth and induces apoptosis in MCF-7 human breast cancer cells. The mechanisms behind these effects may stem from the downregulation of Bcl-2 protein expression and upregulation of Bax expression.

Aberrant expression of microRNA-155 (miR-155) has been reported in several human cancers and is associated with prognosis of patients. However, the clinical significance of miR‑155 and its underlying mechanisms involved in hepatocarcinogenesis remain to be determined. In this study, we demonstrated that the expression of miR-155 was elevated in both hepatocellular carcinoma (HCC) tissues and cell lines. Clinical association analysis revealed that high expression of miR-155 was correlated with malignant clinicopathological characteristics including large tumor size, high Edmondson-Steiner grading and TNM tumor stage. Furthermore, its high expression conferred a reduced 5-year overall survival and disease-free survival of HCC patients. Gain- and loss-of function studies revealed that miR‑155 promoted cell cycle progression, cell proliferation and inhibited apoptosis. Mechanistically, we identified AT-rich interactive domain 2 (ARID2) as a direct downstream target and functional mediator of miR‑155 in HCC cells. Notably, alterations of ARID2 expression abrogated the effects of miR‑155 on HCC cell proliferation, cell cycle and apoptosis. Moreover, we demonstrated that Akt phosphorylation is essential for the functional roles of miR‑155 through altering Cyclin D1 and p27, which were key components of cell cycle machinery. Finally, we disclosed that the downregulation of miR‑155 suppressed tumor growth of HCC by inhibiting Akt signaling pathway. In conclusion, our results indicate that miR‑155 promotes tumor growth of HCC by targeting ARID2-mediated Akt phosphorylation pathway, and potentially serves as a novel prognostic biomarker and therapeutic target for HCC.

Metabolic reprogramme was a key characteristic of malignant tumors. Increased evidences indicated that besides Warburg effect (abnormal glucose metabolism), abnormal lipid metabolism played more and more important in progression and metastasis of malignant tumors. MiR-15a-5p could inhibit development of lung cancer, while its regulating mechanism, especially the role in lipid metabolism still remained unclear. In this study, we confirmed that miR-15a-5p inhibited proliferation, migration and invasion of lung cancer cells. The online analysis of Mirpath v.3 predicted that miR-15a-5p was closely associated with fatty acid synthesis and lipid metabolism. In vitro cell experiments revealed that miR-15a-5p significantly suppressed fatty acid synthesis of lung cancer cells by inhibiting acetate uptake. Extensive analysis indicated that miR-15a-5p could suppress acetyl-CoA activity and decrease histone H4 acetylation by inhibiting ACSS2 expression. In addition, we also observed that ACSS2 located in nucleus under hypoxic conditions, while miR-15a-5p could be transported into nucleus to inhibit the function of ACSS2. Our study unveiled a novel mechanism of miR-15a-5p in inhibiting metastasis of lung cancer cells by suppressing lipid metabolism via suppression of ACSS2 mediated acetyl-CoA activity and histone acetylation.

// Ping Li 1, Jian-bo Fan 2, Yanxia Gao 1, Ming Zhang 1, Li Zhang 1, Ning Yang 1, Xiaojing Zhao 1 1 Department of Emergency, the Second Affiliated Hospital of Xi'an Jiao Tong University, Xi&rsquo;an, China 2 Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, Nantong, China Correspondence to: Xiaojing Zhao, email: Zhao_xiandr@163.com Keywords: miR-135b-5p, Ppm1e, AMPK, LPS, TNF&alpha; Received: September 02, 2016&nbsp;&nbsp;&nbsp;&nbsp; Accepted: October 05, 2016&nbsp;&nbsp;&nbsp;&nbsp; Published: October 25, 2016 ABSTRACT AMPK activation in monocytes could suppress lipopolysaccharide (LPS)-induced tissue-damaging TNFa production. We are set to provoke AMPK activation via microRNA (&ldquo;miRNA&rdquo;) downregulating its phosphatase Ppm1e. In human U937 and THP-1 monocytes, forced expression of microRNA-135b-5p (&ldquo;miR-135b-5p&rdquo;) downregulated Ppm1e and activated AMPK signaling. Further, LPS-induced TNF&alpha; production in above cells was dramatically attenuated. Ppm1e shRNA knockdown in U937 cells also activated AMPK and inhibited TNF&alpha; production by LPS. AMPK activation is required for miR-135b-induced actions in monocytes, AMPK&alpha; shRNA knockdown or T172A dominant negative mutation almost abolished miR-135b-5p&rsquo;s suppression on LPS-induced TNF&alpha; production. Significantly, miR-135b-5p inhibited LPS-induced reactive oxygen species (ROS) production, NF&kappa;B activation and TNF&alpha; mRNA expression in human macrophages. AMPK&alpha; knockdown or mutation again abolished above actions by miR-135b-5p. We conclude that miR-135b-5p expression downregulates Ppm1e to activate AMPK signaling, which inhibits LPS-induced TNF&alpha; production via suppressing ROS production and NF&kappa;B activation.