Silencing of LncRNA HULC Enhances Chemotherapy Induced Apoptosis in Human Gastric Cancer

J Med Biochem. 2016 Apr;35(2):137-143. doi: 10.1515/jomb-2015-0016. Epub 2016 May 9.

Abstract

Background: Gastric cancer (GC) is one of the most common cancers in the world; however, chemoresistance greatly decreases the efficacy of therapy in gastric cancer. Long noncoding RNAs (IncRNAs) participate in a variety of biological processes, and we hypothesize that lncRNA HULC regulates the multidrug resistance in GC treatment.

Methods: We obtained GC tissue samples from 42 GC patients and detected the expression level of HULC in the plasma and tissues via qRT-PCR. The relationship between HULC expression and survival rate was confirmed by Kaplan-Meier survival analysis. We verified the expression of HULC in GC cell lines via qRT-PCR, and the function of HULC was detected via flow cytometry assay and CCK-8 assay.

Results: HULC was highly expressed in the plasma and tissues of the GC patients compared with controls, with HULC high expression indicating lower survival rate. HULC knockdown enhanced cisplatin-induced apoptosis in GC cells.

Conclusions: Our results suggest that silencing lncRNA HULC could enhance chemotherapy induced apoptosis in GC cells, which could provide a novel approach for therapeutic strategies.

Uvod: Karcinom želuca jedan je od najčešćih kancera na svetu. Međutim, rezistencija na hemoterapiju umnogome smanjuje efikasnost lečenja karcinoma želuca. Dugi neko-dirajući RNK (lncRNK) učestvuju u mnogim biološkim pro-cesima i naša je hipoteza da lncRNK HULC reguliše rezistenciju na lekove u terapiji za karcinom želuca.

Metode: Uzeli smo uzorke tkiva karcinoma želuca od 42 obolelih i detektovali nivo ekspresije HULC u plazmi i tkivima putem qRT-PCR. Odnos između ekspresije HULC i stope preživljavanja potvrđen je pomoću Kaplan-Majerove analize preživljavanja. Ekspresiju HULC u čelijskim linijama karcinoma želuca verifikovali smo pomoću qRT-PCR, dok je funkcija HUMC detektovana protočnom citometrijom i testom CCK-8.

Rezultati: HULC je bio veoma izražen u plazmi i tkivima obolelih od karcinoma želuca u poređenju s kontrolom, dok je visoka ekspresija HULC ukazivala na nižu stopu preživljavanja. Pad vrednosti HULC uticao je na pojačanu apoptozu izazvanu cisplatinom u ćelijama karcinoma želuca.

Zaključak: Naši rezultati pokazuju da bi prigušivanje lncRNK HULC moglo podstaći apoptozu izazvanu hemoterapijom u ćelijama karcinoma želuca, što bi moglo otvoriti nov pristup za terapijske strategije.

Keywords: HULC; LncRNA; gastric cancer; multidrug resistance.