Human Canalicular Multispecific Organic Anion Transporter (cMOAT) Is Expressed in Human Lung, Gastric, and Colorectal Cancer Cells

1997 ◽  
Vol 240 (3) ◽  
pp. 606-611 ◽  
Author(s):  
Fumihiko Narasaki ◽  
Mikio Oka ◽  
Reiji Nakano ◽  
Koki Ikeda ◽  
Minoru Fukuda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Human Lung ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Anion Transporter ◽  
Colorectal Cancer Cells

scholarly journals SLCO4A1-AS1 Facilitates the Malignant Phenotype via miR-149-5p/STAT3 Axis in Gastric Cancer Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Qing Li ◽  
Dachuan Zhang ◽  
Hui Wang ◽  
Jun Xie ◽  
Lei Peng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Gastric Cancer Cells ◽  
Anion Transporter ◽  
Transporter Family ◽  
Cancer Tissues ◽  
Development Of Gastric Cancer

Solute carrier organic anion transporter family member 4A1 (SLCO4A1-AS1), a newly discovered lncRNA, may exert effects in tumors. Since its role in gastric cancer remains obscure, we sought to explore the mechanism of SLCO4A1-AS1 in gastric cancer. The relationship among SLCO4A1-AS1, miR-149-5p, and STAT3 was detected by bioinformatics, dual luciferase analysis, and Pearson’s test, and the expressions of these genes were determined by quantitative real-time PCR and Western blot. Moreover, CCK-8, flow cytometry, wound healing assay, and Transwell analysis were performed to verify the function of SLCO4A1-AS1 in gastric cancer. Rescue experiments were used to detect the role of miR-149-5p. The expressions of SLCO4A1-AS1 and STAT3 were increased, while the expression of miR-149-5p was suppressed in gastric cancer tissues and cell lines. In addition, STAT3 expression was negatively correlated with miR-149-5p expression but was positively correlated with SLCO4A1-AS1 expression. Overexpression of SLCO4A1-AS1 promoted cell viability, migration, invasion, and STAT3 expression but suppressed apoptosis, while knockdown of SLCO4A1-AS1 had the opposite effect. SLCO4A1-AS1 bound to miR-149-5p and targeted STAT3. Moreover, miR-149-5p mimic inhibited the malignant development of gastric cancer cells and obviously reversed the function of SLCO4A1-AS1 overexpression. Our research reveals that abnormally increased SLCO4A1-AS1 expression may be an important molecular mechanism in the development of gastric cancer.

scholarly journals CHK1 Inhibition Is Synthetically Lethal with Loss of B-Family DNA Polymerase Function in Human Lung and Colorectal Cancer Cells

2020 ◽  
Vol 80 (8) ◽  
pp. 1735-1747 ◽  
Author(s):  
Rebecca F. Rogers ◽  
Michael I. Walton ◽  
Daniel L. Cherry ◽  
Ian Collins ◽  
Paul A. Clarke ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Dna Polymerase ◽  
Human Lung ◽  
Colorectal Cancer Cells ◽  
Synthetically Lethal

scholarly journals Uremic serum residue decreases SN-38 sensitivity through suppression of organic anion transporter polypeptide 2B1 in LS-180 colon cancer cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shoichi Ozawa ◽  
Masayuki Tsujimoto ◽  
Hitoshi Uchiyama ◽  
Natsuko Ito ◽  
Satoe Morishita ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Organic Anion ◽  
Human Colon ◽  
Organic Anion Transporter ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Anion Transporter ◽  
Uremic Serum

Abstract Pharmacokinetics of SN-38 in patients with end-stage kidney disease (ESKD) is partially varied because of fluctuations in transporters expression and/or function by high protein bound-uremic toxins concentration. The fluctuations may induce variations in anticancer drugs sensitivity to cancer cells. We aimed to clarify the variations in sensitivity of SN-38 to cancer patients with ESKD and investigate this mechanism, by human colon cancer cells exposed to uremic serum residue. LS180 cells were exposed to normal or uremic serum residue (LS/NSR or LS/USR cells) for a month. IC50 values of SN-38 in LS/NSR or LS/USR cells were calculated from viability of each cells treated SN-38. mRNA expression and intracellular SN-38 accumulation was evaluated by RT-PCR and HPLC-fluorescence methods, respectively. The IC50 value in LS/USR cells was higher than that in LS/NSR cells. Organic anion transporter polypeptide (OATP) 2B1 mRNA expression was lower in LS/USR cells than in LS/NSR cells, and SN-38 accumulation in LS/USR cells was lower than that in LS/NSR cells. Only co-treatment baicalin, which is OATP2B1 inhibitor, almost negated the difference in SN-38 accumulation between LS/NSR and LS/USR. Anticancer effects of substrates of OATP2B1, such as SN-38, were reduced in ESKD patients at the same plasma substrate concentration.

Identification of a fluorescent small-molecule enhancer for therapeutic autophagy in colorectal cancer by targeting mitochondrial protein translocase TIM44

Gut ◽  
2016 ◽  
Vol 67 (2) ◽  
pp. 307-319 ◽  
Author(s):  
Yinghui Huang ◽  
Jie Zhou ◽  
Shenglin Luo ◽  
Yang Wang ◽  
Jintao He ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mass Spectrometry ◽  
Rna Sequencing ◽  
Small Molecule ◽  
Biological Effects ◽  
Organic Anion ◽  
Mitochondrial Protein ◽  
Mtor Pathway ◽  
Organic Anion Transporter ◽  
Anion Transporter

ObjectiveAs the modulation of autophagic processes can be therapeutically beneficial to cancer treatment, the identification of novel autophagic enhancers is highly anticipated. However, current autophagy-inducing anticancer agents exert undesired side effects owing to their non-specific biodistribution in off-target tissues. This study aims to develop a multifunctional agent to integrate cancer targeting, imaging and therapy and to investigate its mechanism.DesignA series of mitochondria-targeting near-infrared (NIR) fluorophores were synthesised, screened and identified for their autophagy-enhancing activity. The optical properties and biological effects were tested both in vitro and in vivo. The underlying mechanism was investigated using inhibitors, small interfering RNA (siRNA), RNA sequencing, mass spectrometry and human samples.ResultsWe have screened and identified a new NIR autophagy-enhancer, IR-58, which exhibits significant tumour-selective killing effects. IR-58 preferentially accumulates in the mitochondria of colorectal cancer (CRC) cells and xenografts, a process that is glycolysis-dependent and organic anion transporter polypeptide-dependent. IR-58 kills tumour cells and induces apoptosis via inducing excessive autophagy, which is mediated through the reactive oxygen species (ROS)-Akt-mammalian target of rapamycin (mTOR) pathway. RNA sequencing, mass spectrometry and siRNA interference studies demonstrate that translocase of inner mitochondrial membrane 44 (TIM44)-superoxide dismutase 2 (SOD2) pathway inhibition is responsible for the excessive ROS, autophagy and apoptosis induced by IR-58. TIM44 expression correlates positively with CRC development and poor prognosis in patients.ConclusionsA novel NIR small-molecule autophagy-enhancer, IR-58, with mitochondria-targeted imaging and therapy capabilities was developed for CRC treatment. Additionally, TIM44 was identified for the first time as a potential oncogene, which plays an important role in autophagy through the TIM44-SOD2-ROS-mTOR pathway.

Sign in / Sign up

Export Citation Format

Share Document