Silencing of long non-coding RNA ANRIL inhibits the development of multidrug resistance in gastric cancer cells.
The development of multidrug resistance (MDR) is a crucial cause of therapy failure in gastric cancer, which results in disease recurrence and metastasis. Long non-coding RNAs (lncRNAs) have been proven to be critical in carcinogenesis and metastasis of gastric cancer. However, little is known about the roles of ANRIL (antisense non-coding RNA in the INK4 locus) in gastric cancer MDR. The aim of our study is to identify the biological function of ANRIL in gastric cancer MDR. In our results, ANRIL was highly expressed in gastric cancer tissues of cisplatin-resistant and 5-fluorouracil (5-FU)-resistant patients, and the same upregulation trends were observed in cisplatin-resistant cells (BGC823/DDP) and 5-FU-resistant cells (BGC823/5-FU). In addition, BGC823/DDP and BGC823/5-FU cells transfected with ANRIL siRNA and treated with cisplatin or 5-FU, respectively, exhibited significant lower survival rate, decreased invasion capability, and high percentage of apoptotic tumor cells. The influence of ANRIL knockdown on MDR was assessed by measuring IC50 of BGC823/DDP and BGC823/5-FU cells to cisplatin and 5-FU, the result showed that silencing ANRIL decreased the IC50 values in gastric cancer cells. Moreover, qRT-PCR and western blotting revealed that ANRIL knockdown decreased the expression of MDR1 and MRP1, both of which are MDR related genes; regression analysis showed that the expression of ANRIL positively correlated with the expression of MDR1 and MRP1, resprectively In summary, knockdown of lncRNA ANRIL in gastric cancer cells inhibits the development of MDR, suggesting an efficacious target for reversing MDR in gastric cancer therapy.
Department of Oncology, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, P.R. China.
Wei-Guang
WG
Lan
Department of Oncology, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, P.R. China.
Dian-Hong
DH
Xu
The Second Department of Internal Medicine, People's Hospital of Kenli County, Kenli, Shandong, P.R. China.
Chen
C
Xu
Department of Pharmacy, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, P.R. China.
Chang-Ling
CL
Ding
Department of Oncology, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, P.R. China.
Fang-Ling
FL
Ning
Department of Pharmacy, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, P.R. China.
Yan-Li
YL
Zhou
Department of Oncology, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, P.R. China.
Long-Bo
LB
Ma
Department of Oncology, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, P.R. China.
Chang-Min
CM
Liu
Department of Oncology, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, P.R. China.
Xia
X
Han
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D005472:Fluorouracil / Q000008:administration & dosage; D020868:Gene Silencing / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D034741:RNA, Small Interfering; D013270:Stomach / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015996:Survival Rate; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002945:Cisplatin; D005472:Fluorouracil; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; C561518:CDKN2B antisense RNA, human; C421109:multidrug resistance-associated protein 1