The present study aimed to identify whether microRNA (miRNA/miR)-34a regulates the proliferation and apoptosis of gastric cancer cells by targeting silent information regulator 1 (SIRT1). The expression of miR-34a and SIRT1 and cell viability was investigated in gastric cancer cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was applied to determine miR-34a expression in gastric adenocarcinoma, normal pericarcinomatous tissues, human normal gastric mucosa epithelial cell line GES and various gastric cancer cell strains. A bioinformatics method was then used to predict the target gene of miR-34a. A human miR-34a over expression lentiviral vector system was constructed and then used for transfection of the gastric cancer cell line SCG-7901 to determine the expression of SIRT1 mRNA and SIRT1 protein using RT-qPCR and western blot analysis. The MTT method and flow cytometry was used to measure cell proliferation and apoptosis. The relative expression of miR-34a in gastric cancer tissues was significantly decreased compared with that in normal tissues (P<0.01). miR-34a expression was also significantly decreased in low differentiated N2, N3 gastric cancer tissues (P<0.01). However, tumor size and filtration degree were not significantly associated with miR-34a expression. The relative expression of miR-34a was decreased in gastric cancer cells, especially in the SGC-7901 cell line (P<0.01) compared with the GES group. The relative expression of SIRT1 protein was decreased in the miR-34a group compared with the negative control (P<0.01). The rate of proliferation was significantly decreased, whereas the rate of apoptosis was significantly increased in the miR-34a group compared with the NC group (P<0.01). Therefore, the present results suggested that miRNA-34a serves a pivotal role in gastric cancer as a cancer suppressor gene by targeting SIRT1 to regulate the proliferation and apoptosis of gastric cancer cells.

BACKGROUND: Glycolysis was an essential driver of chemo-resistance in colorectal cancer (CRC), albeit with limited molecular explanations. OBJECTIVE: We strived to elucidate the involvement of lncRNA XIST/miR-137/PKM axis in chemo-tolerance and glycolysis of CRC. METHODS: Altogether 212 pairs of tumor tissues and adjacent normal tissues were collected from CRC patients. Moreover, human CRC epithelial cell lines, including HT29, SW480, SW620 and LoVo, were purchased in advance, and their activity was estimated after transfection of si-XIST or miR-137 mimic. Furthermore, 5-FU/cisplatin-resistance of CRC cells was determined through MTT assay, and glycolytic potential of CRC cells was appraised based on oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). RESULTS: Highly-expressed XIST were predictive of severe symptoms and unfavorable 3-year survival of CRC patients (P< 0.05). Besides, silencing of XIST not only diminished proliferative, migratory and invasive power of CRC cells (P< 0.05), but also enhanced sensitivity of CRC cells responding to 5-FU/cisplatin (P< 0.05). Glycolytic potency of CRC cells was also undermined by si-XIST, with decreased maximal respiration and maximal glycolytic capacity in the si-XIST group as relative to NC group (P< 0.05). Nevertheless, miR-137 mimic attenuated the facilitating effect of pcDNA3.1-XIST on proliferation, migration, invasion, 5-FU/cisplatin-resistance and glycolysis of CRC cells (P< 0.05). Ultimately, ratio of PKM2 mRNA and PKM1 mRNA, despite being up-regulated by pcDNA3.1-XIST, was markedly lowered when miR-137 mimic was co-transfected (P< 0.05). CONCLUSIONS: LncRNA XIST/miR-137 axis reinforced glycolysis and chemo-tolerance of CRC by elevating PKM2/PKM1 ratio, providing an alternative to boost chemo-therapeutic efficacy of CRC patients.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death worldwide. In China, the situation is even worse as cancer incidence and mortality continue to increase rapidly. Although tremendous progress has been made toward HCC treatments, the benefits for liver cancer patients are still limited. Therefore, it is necessary to identify and develop novel therapeutic methods. Neuronally expressed developmentally downregulated 4 (NEDD4), an E3 ubiquitin ligase, plays a critical role in the development and progression of various types of human cancers. In our study, NEDD4 acts as an oncoprotein in both QGY7703 and SMMC7721 liver cancer cell lines. We found that depletion of NEDD4 by siRNA transfection led to inhibition of cell growth, invasion and migration, and promotion of apoptosis. In contrast, overexpression of NEDD4 via plasmid transfection resulted in facilitated cell proliferation, invasion and migration, and decreased apoptosis. Importantly, we observed that tumor suppressor LATS1, also a core component of Hippo pathway, was negatively regulated by NEDD4 in liver cancer cells. Our findings suggested that NEDD4 may be involved in the HCC progression via regulating LATS1 associated signaling pathway. Therefore, targeting NEDD4-LATS1 signaling could be a potential therapeutic option for HCC treatment.

Background Considering the boosting effect of glycolysis on tumor chemoresistance, this investigation aimed at exploring whether miR‐488/PFKFB3 axis might reduce drug resistance of colorectal cancer (CRC) by affecting glycolysis, proliferation, migration, and invasion of CRC cells. Method Totally, 288 CRC patients were divided into metastasis/recurrence group (n = 107) and non‐metastasis/recurrence group (n = 181) according to their prognosis about 1 year after the chemotherapy, and their 3‐year overall survival was also tracked. Besides, miR‐488 expression was determined in peripheral blood of CRC patients and also in CRC cell lines (ie, W620, HT‐29, Lovo, and HCT116). The targeted relationship between miR‐488 and PFKFB3 was predicted by Targetscan software and confirmed by dual‐luciferase reporter gene assay. Moreover, glycolysis and drug tolerance of CRC cells lines were assessed. Results MiR‐488 expression was significantly decreased in metastatic/recurrent CRC patients than those without metastasis/recurrence (P < .05), and lowly expressed miR‐488 was suggestive of unfavorable 3‐year survival, large tumor size, poor differentiation, in‐depth infiltration, and advanced Duke stage of CRC patients (P < .05). Besides, CRC cell lines transfected by miR‐488 mimic demonstrated decreases in glucose uptake and lactate secretion, increases in oxaliplatin/5‐Fu‐sensistivity, as well as diminished capability of proliferating, invading, and migratory (P < .05), which were reversible by extra transfection of pcDNA3.1‐PFKFB3 (ie, miR‐488 mimic + pcDNA3.1‐PFKFB3 group). Finally, the mRNA level of PFKFB3 was down‐regulated by miR‐488 mimic in CRC cell lines after being targeted by it (P < .05). Conclusion The miR‐488/PFKFB3 axis might clinically refine chemotherapeutic efficacy of CRC, given its modifying glycolysis and metastasis of CRC cells.

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