Non-Hodgkin's lymphoma (NHL) is a malignant tumor originated in lymphatic hematopoietic tissue. At present, chemotherapy is the main treatment method of NHL, but the chemoresistance is still an important reason for NHL treatment failure. The mechanism of NHL multidrug resistance (MDR) is complex, involving a variety of singnal pathways, in which mutation in the genetic level of the key genes can result in tumor cell resistance phenomenon. MicroRNA are small non-coding RNA that can be widely detected in plants,animal species and viruses. They regulate protein expression by repressing translation mRNA target at the post-transcriptional level, participating in the differentiation and development of tumor cells, as well as the occurrence and development of tumor, the change of the expression level microRNA plays an important role in the genesis and chemoresistance mechanism of NHL. Therefore, the intervening factitiously the expression level of microRNA in NHL through manufacturing antisense oligonucleotide (AMO) or using substitution of microRNA, changing the expression level of their target protein, and combining with the therapy of NHL, there will be an guiding significance in reversing the drug and radiation resistance of NHL, thus improving its poor prognosis. This article reviews the microRNAs closely related with drug and radiation resistance of NHL, and their potential targets. Furthermore, the specific role of these microRNAs in the genesis and chemoresistance mechanism of NHL are deeply elaborated.
Animals ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Lymphoma, Non-Hodgkin ; drug therapy ; genetics ; MicroRNAs ; genetics

OBJECTIVETo explore the relationship between microRNA and drug resistance in leukemia treatment by screening and identifying the microRNAs which differentially express in K562 cell line and its adriamycin resistant cells-K562/A02 cell line.

METHODSThe drug resistance potency of K562/A02 cells was evaluated by MTT assay. P-gp expression of K562 and K562/A02 cells were detected by flow cytometry (FCM). The differentially expressed microRNAs in K562 and K562/A02 cells were analyzed by microarray technique and Real Time RT-PCR.

RESULTSThe resistance to adriamycin (ADM) of K562/A02 cells was 180 fold greater than that of K562 cells. P-gp expression rate of K562 and K562/A02 cells was 0.2% and 86%, respectively. Twenty-two microRNAs expressed differentially in K562 and K562/A02 cells (P < 0.01). As compared to K562 cells, expressions of miR-221, miR-155 and miR-451 were up-regulated by more than two fold, while expression of miR-98, miR-181a, let-7f, let-7g, miR-424 and miR-563 down-regulated by more than two fold in K562/A02 cells. The results of real time RT-PCR were consistent with that of microarray. Of note, differential expressions of miR-451, miR-155, miR-221, let-7f and miR-424 were remarkable.

CONCLUSIONK562/A02 cells show a different microRNA expression profile as compared to its parental K562 cells, suggesting microRNAs including miR-221, miR-155, miR-451, let-7f and miR-424 may be involved in the mechanism of drug resistance in leukemia. These differentially expressed microRNAs provide potential novel targets for overcoming drug-resistance.

Doxorubicin ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; genetics ; Humans ; K562 Cells ; MicroRNAs ; genetics

Multidrug resistance-related proteins (MRP) are identified as ATP-dependent efflux pumps, the expression abnormality of which has close relationship with multidrug resistance (MDR) in a variety kinds of malignancies, leading to the failure of chemotherapy. The relationship between the expression of MRP and acute leukemia remains to be proved, since experiments and clinical researches are still insufficient. In this article, the structure, distribution, function, and relation of MRP to MDR and prognosis of acute leukemia are reviewed.
Acute Disease ; Drug Resistance, Multiple ; genetics ; Drug Resistance, Neoplasm ; genetics ; Genes, MDR ; Humans ; Leukemia ; genetics ; Proteins ; genetics

OBJECTIVE: To detect the differential expressions of miR-451, ABCB1 and ABCC2 in drug-sensitive leukemia cell line K562 and drug-resistant cell line K562/A02, and explore the regulatory relationship between miR-451 and the expressions of ABCB1 and ABCC2 , and the mechanism of miR-451 involved in drug resistance in leukemia. METHODS: CCK-8 assay was used to detect the drug resistance of K562/A02 and K562 cells. Quantitative Real-time PCR (qRT-PCR) was used to verify the differential expressions of miR-451 in K562 and K562/A02 cells. MiR-451 mimic and negative control (miR-NC), miR-451 inhibitor and negative control (miR-inNC) were transfected into K562 and K562/A02 cells respectively, then qRT-PCR and Western blot were used to detect the expression levels of mRNA and protein of ABCB1 and ABCC2 in K562 and K562/A02 cells and the transfected groups. RESULTS: The drug resistance of K562/A02 cells to adriamycin was 177 times higher than that of its parent cell line K562. Compared with K562 cells, the expression of miR-451 in K562/A02 cells was significantly higher (P <0.001), and the mRNA and protein expression levels of ABCB1 and ABCC2 in K562/A02 cells were significantly higher than those in K562 cells (P <0.001). After transfected with miR-451 inhibitor, the expression of miR-451 was significantly down-regulated in K562/A02 cells (P <0.001), the sensitivity to chemotherapy drugs was significantly enhanced (P <0.05), and the mRNA and protein expressions of ABCB1 and ABCC2 were significantly decreased (P <0.01). After transfected with miR-451 mimic, the expression of miR-451 was significantly upregulated in K562 cells (P <0.001), and the mRNA and protein expressions of ABCB1 and ABCC2 were significantly increased (P <0.01). CONCLUSION There are significant differences in the expressions of miR-451, ABCB1 and ABCC2 between the drug-sensitive leukemia cell line K562 and drug-resistant cell line K562/A02, which suggests that miR-451 may affect the drug resistance of leukemia cells by regulating the expression of ABCB1 and ABCC2.
Humans ; K562 Cells ; Drug Resistance, Neoplasm/genetics* ; Drug Resistance, Multiple/genetics* ; Doxorubicin/pharmacology* ; MicroRNAs/genetics* ; Leukemia/genetics* ; RNA, Messenger

Cell Line, Tumor ; Drug Resistance, Multiple ; genetics ; Drug Resistance, Neoplasm ; genetics ; Humans ; Microbubbles ; Oligoribonucleotides, Antisense ; genetics ; Transfection ; methods ; Ultrasonics

Chemotherapy remains at the first line for the treatment of leukemia. However, the multi-drug resistance of the tumor cells caused by chemotherapeutic drugs has seriously affected the effect of chemotherapy. And this is the main reason for the failure of the leukemia treatment. Therefore, to explore an effective way of reversing drug resistance has become the key of leukemia treatment. RNA interference, a system within living cells, helps to determine which genes are active and how active they are. It is a process in which translation of some cell messenger RNA (mRNA) sequences is prevented, because of the presence of (and consequent destruction of) matching double-stranded RNA sequences. RNA interference is also called post-transcriptional gene silencing (PTGS), since its effect on gene expression occurs after the production of mRNA during transcription. It is believed that RNA interference can protect the cell against viruses and other threats. The greatest advantage of RNAi is the specificity and high efficiency which can induce suppression of specific genes of interest but the unrelated genes are not affected. The selective and robust effect of RNAi on gene expression makes it a valuable research tool both in cell culture and living organisms because synthetic dsRNA introduced into cells can induce the suppression of specific genes of interest. Nowadays, the technology has been widely used in biomedical fields, especially in the diagnosis and treatment of blood system disease. However, besides the stability, targeting and biological safety in genetics, the immune response induced by exogenous RNA is also one of the key factors to limit the clinical practice of this emerging technology. In this review, the breakthrough of the technology in multi-drug resistance reversal in leukemia is summarized with the RNA interference technology as a starting point.
Cell Line, Tumor ; Drug Resistance, Multiple ; genetics ; Drug Resistance, Neoplasm ; genetics ; Gene Silencing ; Humans ; Leukemia ; genetics ; therapy ; RNA Interference

OBJECTIVETo analyze the difference in microRNAs expression between MCF-7 and MCF-7/ADR cells and explore the association between microRNA and drug resistance of breast cancer.

METHODSThe drug resistance of MCF-7/ADR cells was evaluated using MTT assay and flow cytometry. Microarray technique and RT-PCR were used to analyze the differential expressions of the microRNA between MCF-7 and MCF-7/ADR cells.

RESULTSThe drug resistance index of MCF-7/ADR cells relative to the parental MCF-7 cells was 33.2. The percentages of the side population in MCF-7/ADR and MCF-7 cells were (9.50-/+0.9)% and (0.85-/+0.2)%, respectively. Microarray analysis of MCF-7 to MCF-7/ADR cells identified 36 differentially expressed genes, including 16 up-regulated and 20 down-regulated genes in MCF-7/ADR cells. RT-PCR identified 14 microRNAs that were differentially expressed between MCF-7 and MCF-7/ADR cells, including 7 up-regulated and 7 down-regulated ones in MCF-7/ADR cells. Of these differentially expressed microRNAs, mir-221, mir222, mir-130a, and mir-155 showed significantly increased expression, and mir200a, mir-200b, mir-200c, and mir-421 showed significantly lowered expression in MCF-7/ADR cells as indicated by the results of microarray analysis and RT-PCR.

CONCLUSIONMCF-7/ADR cells show a different microRNA expression profile from its parental MCF-7 cells, suggesting the involvement of microRNAs in tumor cell drug resistance. This finding provides a experimental basis for further study of mechanism underlying the drug resistance of breast cancer.

Breast Neoplasms ; genetics ; Doxorubicin ; pharmacology ; Drug Resistance, Neoplasm ; genetics ; Female ; Humans ; MicroRNAs ; genetics ; Tumor Cells, Cultured

Lung cancer is the leading cause of cancer-related deaths worldwide. Targeted therapy is beneficial in most cases, but the development of drug resistance stands as an obstacle to good prognosis. Multiple mechanisms were explored such as genetic alterations, activation of bypass signaling, and phenotypic transition. These intrinsic and/or extrinsic dynamic regulations facilitate tumor cell survival in meeting the demands of signaling under different stimulus. This review introduces lung cancer plasticity and heterogeneity and their correlation with drug resistance. While cancer plasticity and heterogeneity play an essential role in the development of drug resistance, the manipulation of them may bring some inspirations to cancer prognosis and treatment. That is to say, lung cancer plasticity and heterogeneity present us with not only challenges but also opportunities.
Carcinoma, Non-Small-Cell Lung ; genetics ; metabolism ; Drug Resistance, Neoplasm ; genetics ; Humans ; Lung Neoplasms ; genetics ; metabolism

The aim of this study was to investigate the potential benefit of combination therapy with 5-bromotetrandrine (5-BrTet) and daunorubicin (DNR) on chronic leukemia. The apoptosis of K562/A02 cells treated by DNA, BrTet and BrTet combined with DNR for 48 hours was detected by flow cytometry; the expressions levels of survivin mRNA and protein K562/A02 cells treated by DNR, BrTet and BrTet combined with DNR and in untreated K562 cells for 48 hours were measured by RT-PCR and Western blot respectively. The results showed that the combination of BrTet with DNR increased apoptotic rate of K562/A02, down-regulated the expression levels of survivin mRNA and protein in K562/A02 cells as compared with blank control and cells treated by BrTet or DNR alone, the survivin expression in K562/A02 cells was higher than that in K562 cells. It is concluded that the combination of BrTet with DNR can effectively reverse the multidrug resistance of K562/A02 cells, promote the apoptosis of K562/A02 cells, the mechanism of which may be related with down-regulation of survivin expression. Survivin may be a target for the treatment of MDR in hematopoietic malignancies.
Apoptosis ; drug effects ; genetics ; Benzylisoquinolines ; pharmacology ; Daunorubicin ; pharmacology ; Drug Resistance, Multiple ; genetics ; Drug Resistance, Neoplasm ; genetics ; Gene Expression Regulation, Leukemic ; Humans ; Inhibitor of Apoptosis Proteins ; genetics ; K562 Cells

OBJECTIVE: To study the expression and function of long non-coding RNA linc00467 in childhood acute myeloid leukemia (AML). METHODS: Bone marrow samples were collected from 5 children with AML who were diagnosed from May 2016 to June 2018. Normal bone marrow samples based on bone marrow examination were collected from 3 children as controls. Quantitative real-time PCR was used to measure the expression of linc00467 in the two groups. A lentivirus system was used to achieve overexpression of linc00467 in AML cells (HL-60) (linc00467 overexpression group), and empty vector expressing green fluorescent protein (GFP) was transfected into AML cells to establish a GFP control group. A lentivirus system was used to insert an interfering sequence into AML cells (sh-linc00467 interfering group), and a random sequence was inserted to establish an sh-NC control group. Cell proliferation and resistance to doxorubicin were observed for all groups. RESULTS: Compared with the normal control group, the children with AML had a significant increase in linc00467 (P=0.018). Overexpression and interference with linc00467 expression had no significant effect on cell proliferation. Compared with the GFP control group, the linc00467 overexpression group had a significant increase in the viability of HL-60 cells at the adriamycin concentrations of 0.1, 0.2, 0.3, 0.4, and 0.5 μg/mL (P<0.05). Compared with the sh-NC control group, the sh-linc00467 interfering group had a significant reduction in the viability of HL-60 cells at the adriamycin concentrations of 0.1, 0.2, 0.3, 0.4, and 0.5 μg/mL (P<0.05). Compared with the untreated group, the adriamycin treatment group had a significant increase in the expression of linc00467 in HL-60 cells (P<0.05). CONCLUSIONS This study reveals the biological function of linc00467 to promote the resistance to adriamycin in AML, which provides a basis for developing new therapeutic drugs for AML.
Cell Proliferation ; Child ; Drug Resistance, Neoplasm ; Humans ; Lentivirus ; Leukemia, Myeloid, Acute ; genetics ; RNA, Long Noncoding ; genetics