[Knock-down of long noncoding RNA H19 (lncRNA H19) promotes human colorectal cell autophagy and inhibits cell apoptosis induced by lipopolysaccharide].

Objective To investigate the expression levels of lncRNA H19 in ulcerative colitis (UC) patients and its role in UC. Methods Colonic mucosa and serum samples were collected from 25 UC patients and 25 healthy individuals at the General Hospital of Xizang Military Region. The expression levels of lncRNA H19 were detected, and the receiver operating characteristic (ROC) curve analysis was performed using serum samples. An in vitro inflammatory model was established in HT29 colorectal cells under lipopolysaccharide (LPS) stimulation, and the expression levels of lncRNA H19 were observed in HT29 cells through fluorescence quantitative PCR. HT29 cells with downregulated lncRNA H19 was constructed using lentivirus-mediated shRNA. The effect of lncRNA H19 on cell survival was analyzed through MTT assay. Cell apoptosis was detected by flow cytometry, and the protein expression levels of apoptosis and autophagy markers were analyzed through Western blot. After treatment with rapamycin, the survival of HT29 cells was observed by MTT assay. Results lncRNA H19 was highly expressed in the colonic mucosa and serum samples of UC patients with the ROC area being 0.786. Following LPS stimulation, the expression levels of lncRNA H19 was significantly increased in a time-dependent manner. Downregulation of lncRNA H19 can promote cell survival, inhibit cell apoptosis and increase autophagy level in HT29 cells. Treatment with rapamycin significantly increased the cell survival rate. Conclusion Knock-down of lncRNA H19 increases autophagy levels, inhibits LPS-induced apoptosis and promotes the survival of colon cells.

LAMP2A overexpression in colorectal cancer promotes cell growth and glycolysis via chaperone­mediated autophagy.

Lysosome-associated membrane protein type 2A (LAMP2A) is a key protein in the chaperone-mediated autophagy (CMA) pathway and has been demonstrated to be involved in the pathogenesis of a number of tumors. However, the role of CMA in colorectal cancer cell proliferation, metastasis and cell survival during oxidative stress and oxaliplatin resistance remains to be elucidated. In the present study, elevated expression of LAMP2A was observed in colon cancer tissues. Then, CMA activity was increased in SW480 and HT29 colorectal cancer cells with a LAMP2A overexpression vector and CMA activity was decreased using a LAMP2A short interfering RNA vector. MTT and colony formation assays showed that the colorectal cancer cell proliferation ability and cell viability following treatment with H2O2 or oxaliplatin were decreased significantly after LAMP2A knockdown and increased significantly after LAMP2A overexpression. Wound healing assays and Transwell invasion assays demonstrated that downregulation of LAMP2A expression inhibited the cell migration and invasion abilities of colorectal cancer and that upregulation of LAMP2A expression promoted cell migration and invasion. Extracellular acidification rate (ECAR) assay and lactate determination assay showed that glycolysis in colorectal cancer cells was significantly downregulated after LAMP2A knockdown and significantly upregulated after LAMP2A overexpression. Inhibition of glycolysis by 2-DG markedly attenuated LAMP2A-induced chemoresistance in colorectal cancer cells. Collectively, these data indicated that CMA can promote colorectal cancer cell proliferation, metastasis and cell survival during oxidative stress and oxaliplatin resistance and that the mechanism is related to the glycolytic pathway, which may provide a new therapeutic target for colorectal cancer patients.

[Knockdown of hexokinase 2 (HK2) inhibits breast cancer cell proliferation and reduces their resistance to fluorouracil].

Objective To investigate the effect of knocking down hexokinase 2 (HK2) on the proliferation and drug resistance of breast cancer cells and its mechanism. Methods The MDA-MB-231 breast cancer cells were transfected with the short hairpin RNA (shRNA) plasmid. The mRNA and protein levels of HK2 were detected by real-time quantitative PCR and Western blotting, respectively; MTT assay was used to detect the effect of HK2 on the proliferation and 5-fluorouraci (5-FU) resistance of breast cancer cells; Lactate assay and extracellular acidification rate (ECAR) were used to detect the effect of HK2 on the glycolysis of breast cancer cells. Results The breast cancer cell line with stable & low expression of HK2 was obtained, and the mRNA and protein levels of HK2 were significantly reduced. Knockdown of HK2 significantly inhibited the proliferation of breast cancer cells and enhanced the killing effect of 5-FU on them. Down regulation of HK2 significantly inhibited the lactate secretion and lowered the glycolysis baseline in breast cancer cells. Conclusion Knockdown of HK2 inhibits the proliferation of MDA-MB-231 breast cancer cells and reduce their resistance to 5-FU.

Malignant syndromes: current advances.

Introduction: Many drugs are known to induce malignant syndromes. The most common malignant syndromes are induced by the use of antipsychotics and anesthetics and the withdrawal of anti-Parkinson drugs. As the clinical manifestations of antipsychotic malignant syndrome, Parkinson's disease hyperpyrexia syndrome and anesthetic-induced malignant syndrome are very similar, they are easily confused in the clinic.Areas covered: We reviewed articles published between 1960 and April 2021 describing malignant syndromes. This paper provides a detailed literature review of malignant syndromes and important guidance for the diagnosis and treatment of malignant syndromes to clinicians.Expert opinion: Although malignant syndromes are rare conditions with a low incidence, these conditions usually progress rapidly and can endanger patients' lives, meriting attention from clinicians. The typical clinical manifestations of malignant syndromes are hyperpyrexia, muscular rigidity, an altered mental status and increased levels of creatine kinase; however, the pathophysiology, treatment and prognosis of different malignant syndromes are quite different. Prompt diagnosis and treatment may significantly improve the prognosis of patients with malignant syndromes.