Search

Hepatocellular carcinoma (HCC) is one of the most common tumors, so far, there still aren’t good therapeutic methods. Looking for new targets makes a top priority. In this study, we found a OCT4 pseudogene, POU5F1B was significantly upregulated in HCC cells and tissues, patients with high POU5F1B had shorter survival time compared to patients with low POU5F1B expression. POU5F1B overexpression promoted HCC proliferation, while its knockdown inhibited HCC proliferation determined by MTT assay, soft agar growth assay, BrdU incorporation assay, and cell cycle assay. Mechanism analysis suggested POU5F1B could activate AKT, AKT inhibition in HCC cells with POU5F1B overexpression significantly inhibited cell proliferation compared to cells only with POU5F1B overexpression, suggesting POU5F1B promoted HCC proliferation by activating AKT. Finally, we analyzed the relationship between POU5F1B expression and AKT activity in HCC tissues, and found POU5F1B expression was positive correlated with activated AKT. Taken together, our findings suggested POU5F1B promoted HCC proliferation by activating AKT, and provided a new target for HCC therapy. [ABSTRACT FROM AUTHOR]

Abstract: In mammalian cells, E2F family of transcription factors (E2Fs) traditionally modulates assorted cellular functions related to cell cycle progression, proliferation, apoptosis and differentiation. Eight members, E2F1 E2F8 have been recognized of this family so far, and the members of this family are generally divided into activator E2F (E2F1––E2F3a), repressor E2F (E2F3b––E2F5) and inhibitor E2F (E2F6––E2F8) subclasses based on their structur–e and function. Studies have showed that the mammalian E2F family members represent a recent evolutionary adaptation to malignancies besides hepatocellular carcinoma (HCC), and a growing body of evidence has validated that the individual members of the family develop a close relationship with HCC. E2F1 was identified to play overlapping roles in HCC, while E2F2––E2F8 (except E2F6 and E2F7) showed to be tumor-promoter in HCC. However, the mechanism underlying the mammalian E2Fs associated with HCC is still unknown and needs further research. The aim of this review is to sum up the collective knowledge of E2F family and the roles of each member of this family in HCC. Moreover, we will discuss some novel therapeutic target for HCC based on the complicated functions of mammalian E2Fs. [Copyright &y& Elsevier]

Liver cancer (LC) is the leading cause for tumor-related death worldwide, and microRNAs (miRs) have been demonstrated to regulate the progression of LC. In the current study, the function of miR-660 in LC cells was investigated, and the results indicated that miR-660 was highly expressed in LC tissues and cells. This increased expression promoted LC cell proliferation and increased the percentage of S phase cells, while miR-660 knockdown inhibited cell proliferation and increased the percentage of G0/G1 phase cells. A Ser/Thr phosphatase protein phosphatase 2 regulatory subunit βα (PPP2R2A) was indicated as the target of miR-660, and miR-660 could inhibit PPP2R2A levels. The luciferase reporter assay suggested that miR-660 directly bound to the 3'-untranslated region of PPP2R2A. Additionally, it was revealed that miR-660 inhibited p21 expression and promoted cyclin D1 expression, confirming that miR-660 regulated LC cell proliferation by regulating cell cycle progression. The double knockdown of miR-660 and PPP2R2A promoted LC cell proliferation, suggesting that miR-660 promoted LC proliferation by targeting PPP2R2A. [ABSTRACT FROM AUTHOR]

Both mitochondrial morphology and the level of cytosolic calcium [Ca2+]c are actively changed and play critical roles in a number of malignancies. However, whether communications existed between these two processes to ingeniously control the malignant phenotype are far from clear. We investigated the reciprocal regulation between mitochondrial fission and cytosolic calcium signaling in human hepatocellular carcinoma (HCC) cells. Furthermore, the underlying molecular mechanisms and the synergistic effect on autophagy were explored. Our results showed that mitochondrial fission increased the [Ca2+]c and calcium oscillation in HCC cells. We further found that mitochondrial fission-mediated calcium signaling was dependent on ROS-activated NF-κB pathways, which facilitated the expression of STIM1 and subsequent store-operated calciumentry. Additionally, we also demonstrated that increase in [Ca2+]c promoted mitochondrial fission by up-regulating expression of Drp1 and FIS1 via transcription factors NFATC2 and c-Myc, respectively. Moreover, the positive feedback loop significantly promoted HCC cell global autophagy by Ca2+/CAMKK/AMPK pathway. Our data demonstrate a positive feedback loop between mitochondrial fission and cytosolic calcium signaling and their promoting role in autophagy of HCC cells, which provides evidence for this loop as a potential drug target in tumor treatment. [ABSTRACT FROM AUTHOR]