Upregulated lncRNA CACNA1G-AS1 aggravates the progression of colorectal cancer by downregulating p53. Wei L-J,Bai D-M,Wang Z-Y,Liu B-C European review for medical and pharmacological sciences OBJECTIVE:To investigate the role of long non-coding RNA (lncRNA) CACNA1G-AS1 in regulating proliferative and invasive abilities of colorectal cancer (CRC) cells by mediating p53, thus influencing the progression of CRC. PATIENTS AND METHODS:CACNA1G-AS1 level in CRC tissues and adjacent normal tissues was first determined. Its level in CRC patients with different tumor stages was detected as well. Changes in proliferative and invasive abilities of HCT116 and SW480 cells influenced by CACNA1G-AS1 were evaluated. Subcellular distribution of CACNA1G-AS1 was analyzed. Through Western blot, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP) assay, the interaction between CACNA1G-AS1 and EZH2 was assessed. The biological function of the target gene of CACNA1G-AS1 was finally explored. RESULTS:CACNA1G-AS1 was upregulated in CRC tissues compared to adjacent normal ones. Its level remained higher in CRC patients with stage III-IV compared to those with stage I-II. Knockdown of CACNA1G-AS1 reduced proliferative and invasive abilities of HTC116 and SW480 cells. CACNA1G-AS1 was mainly distributed in the nucleus. Moreover, CACNA1G-AS1 was verified to interact with EZH2. Knockdown of CACNA1G-AS1 or EZH2 upregulated p53 level and decreased the recruitment ability of EZH2 on p53. Finally, p53 knockdown could partially reverse the regulatory effect of CACNA1G-AS1 on the proliferative ability of HCT116 cells. CONCLUSIONS:CACNA1G-AS1 downregulates p53 level by forming a carcinogenic complex with EZH2, thereby enhancing the proliferative and invasive abilities of CRC cells. 10.26355/eurrev_202001_19902

Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Maddocks Oliver D K,Berkers Celia R,Mason Susan M,Zheng Liang,Blyth Karen,Gottlieb Eyal,Vousden Karen H Nature Cancer cells acquire distinct metabolic adaptations to survive stress associated with tumour growth and to satisfy the anabolic demands of proliferation. The tumour suppressor protein p53 (also known as TP53) influences a range of cellular metabolic processes, including glycolysis, oxidative phosphorylation, glutaminolysis and anti-oxidant response. In contrast to its role in promoting apoptosis during DNA-damaging stress, p53 can promote cell survival during metabolic stress, a function that may contribute not only to tumour suppression but also to non-cancer-associated functions of p53. Here we show that human cancer cells rapidly use exogenous serine and that serine deprivation triggered activation of the serine synthesis pathway and rapidly suppressed aerobic glycolysis, resulting in an increased flux to the tricarboxylic acid cycle. Transient p53-p21 (also known as CDKN1A) activation and cell-cycle arrest promoted cell survival by efficiently channelling depleted serine stores to glutathione synthesis, thus preserving cellular anti-oxidant capacity. Cells lacking p53 failed to complete the response to serine depletion, resulting in oxidative stress, reduced viability and severely impaired proliferation. The role of p53 in supporting cancer cell proliferation under serine starvation was translated to an in vivo model, indicating that serine depletion has a potential role in the treatment of p53-deficient tumours. 10.1038/nature11743