Significance of miR-15a-5p and CNKSR3 as Novel Prognostic Biomarkers in Non-Small Cell Lung Cancer.

BACKGROUND: In recent years, targeted cancer treatment methods at various molecular levels have been developed for Non-Small Cell Lung Cancer (NSCLC), one of two major subtypes of lung cancer. miRNAbased clinical trials are currently the preferred targeted therapeutic strategy. Also, ceRNAs (competing endogenous RNA) would be the newest and the most effective approach to uncover novel interactions between mRNAs and miRNAs in NSCLC carcinogenesis. There are many factors influencing the efficiency of a miRNA to suppress or silence translation of the target mRNA. The most effective event is the presence of other RNAs showing ceRNA activity. These RNAs contain binding sites for specific miRNAs and enable miRNAs to bind these pseudo targets, instead of the original binding sites on the target mRNA. Therefore, the mRNA of the target gene is less affected by this miRNA, while the amount of miRNA remains the same in the media. METHOD: For this project, we determined that five clinically important different oncogenes (PDL1, FGFR1, DDX3X, SLC1A5, FXR1 ) are involved in the pathogenesis of NSCLC. For this purpose, we transfected model NSCLC cell line, A549, with miRNAs (miR-150-5p, miR-15a-5p, miR-503-5p) targeting these oncogenes to investigate whether these oncogenes will be suppressed at the mRNA level and also how the suppression efficiency of these miRNA on the oncogenes will be affected by possible ceRNA (CNKSR3, POU2F1, HIPK2) activities. RESULTS: miR-15a-5p was determined to have the most suppressive effect on the five genes and three potential ceRNAs (p<0.05). Furthermore, CNKSR3 was the ceRNA most affected by all three miRNAs (p<0.05). CONCLUSION: CNKSR3 was affected more than the oncogenes known to act on NSCLC and this might make it a stronger and novel marker for use in possible treatment regimens designed using miR-15a-5p silencing effect on oncogenes in NSCLC pathogenesis. According to the literature, this is the first study associating NSCLC with miR-15a-5p and CNKSR3.

trans-Bis[2-(piperazin-1-yl)-ethan-amine]-bis-(saccharinato)cobalt(II).

In the centrosymmetric title complex, [Co(C(7)H(4)NO(3)S)(2)(C(6)H(15)N(3))(2)], the Co(II) ion is coordinated by two saccharinate (sac) anions and two neutral 2-piperazin-1-ylethanamine (ppzea) ligands, showing a distorted octa-hedral coordination. Sac is O-bonded via the carbonyl group, while ppzea acts as an N,N'-bidentate chelating ligand. The mol-ecules are connected by N-H⋯N and N-H⋯O hydrogen bonds, forming a linear chain running parallel to the crystallographic a axis. The compound is isostructural with the reported Ni, Zn, and Cd analogues.

Bis(2-pyridylmethanol)bis(saccharinato)zinc(II) and -cadmium(II) at 120 K: three-dimensional structures containing both N-and O-coordinated ambidentate saccharinate ligands.

The title complexes [M(sac)(2)(mpy)(2)] [sac is saccharinate (C(7)H(4)NO(3)S) and mpy is 2-pyridylmethanol (C(6)H(7)NO)], with M = Zn(II) and Cd(II), are isostructural and consist of neutral molecules. The Zn(II) or Cd(II) cations are octahedrally coordinated by the two neutral mpy and two anionic sac ligands. The mpy ligand acts as a bidentate donor through the amine N and hydroxyl O atoms. The sac ligands exhibit an ambidentate coordination behaviour; one is N-coordinated and the other is O-coordinated within the same coordination octahedron. The crystal packing is determined by C-H...O-type hydrogen bonding, as well as by weak py-py and sac-sac aromatic pi-pi-stacking interactions.

Bis(pyridine-2,6-dimethanol-N,O,O')cobalt(II) and -copper(II) disaccharinate dihydrate: three-dimensional structures with extensive hydrogen bonds and aromatic pi-pi-stacking interactions.

Bis(pyridine-2,6-dimethanol-N,O,O')cobalt(II) disaccharinate dihydrate, [Co(C7H9NO2)2](C7H4NO3S)2*2H2O, (I), and bis(pyridine-2,6-dimethanol-N,O,O')copper(II) disaccharinate dihydrate, [Cu(C7H9NO2)2](C7H4NO3S)2*2H2O, (II), collectively [M(dmpy)2](sac)2*2H2O (where M is Co(II) or Cu(II), sac is the saccharinate anion and dmpy is pyridine-2,6-dimethanol), are isostructural. The [M(dmpy)2]2+ cations exhibit distorted octahedral geometry in which the two neutral dmpy species act as tripodal N,O,O'-tridentate ligands. The crystal packing is determined by hydrogen bonding, as well as by weak pyridine-saccharinate pi-pi-stacking interactions.