DNA damage responsive miR-33b-3p promoted lung cancer cells survival and cisplatin resistance by targeting p21WAF1/CIP1

Cisplatin is the most potent and widespread used chemotherapy drug for lung cancer treatment. However, the development of resistance to cisplatin is a major obstacle in clinical therapy. The principal mechanism of cisplatin is the induction of DNA damage, thus the capability of DNA damage response (DDR) is a key factor that influences the cisplatin sensitivity of cancer cells. Recent advances have demonstrated that miRNAs (microRNAs) exerted critical roles in DNA damage response; nonetheless, the association between DNA damage responsive miRNAs and cisplatin resistance and its underlying molecular mechanism still require further investigation. The present study has attempted to identify differentially expressed miRNAs in cisplatin induced DNA damage response in lung cancer cells, and probe into the effects of the misexpressed miRNAs on cisplatin sensitivity. Deep sequencing showed that miR-33b-3p was dramatically down-regulated in cisplatin-induced DNA damage response in A549 cells; and ectopic expression of miR-33b-3p endowed the lung cancer cells with enhanced survival and decreased γH2A.X expression level under cisplatin treatment. Consistently, silencing of miR-33b-3p in the cisplatin-resistant A549/DDP cells evidently sensitized the cells to cisplatin. Furthermore, we identified CDKN1A (p21) as a functional target of miR-33b-3p, a critical regulator of G1/S checkpoint, which potentially mediated the protection effects of miR-33b-3p against cisplatin. In aggregate, our results suggested that miR-33b-3p modulated the cisplatin sensitivity of cancer cells might probably through impairing the DNA damage response. And the knowledge of the drug resistance conferred by miR-33b-3p has great clinical implications for improving the efficacy of chemotherapies for treating lung cancers.     

MicroRNA-29b-3p promotes 5-fluorouracil resistance via suppressing TRAF5-mediated necroptosis in human colorectal cancer

Drug resistance in colorectal cancer is a great challenge in clinic. Elucidating the deep mechanism underlying drug resistance will bring much benefit to diagnosis, therapy and prognosis in patients with colorectal cancer. In this study, miR-29b-3p was shown to be involved in resistance to 5-fluorouracil (5-FU)-induced necroptosis of colorectal cancer. Further, miR-29b-3p was shown to target a regulatory subunit of necroptosis TRAF5. Rescue of TRAF5 could reverse the effect of miR-29b-3p on 5-FU-induced necroptosis, which was consistent with the role of necrostatin-1 (a specific necroptosis inhibitor). Then it was demonstrated that miR-29b-3p was positively correlated with chemoresistance in colorectal cancer while TRAF5 negatively. In conclusion, it is deduced that miR-29b-3p/TRAF5 signaling axis plays critical role in drug resistance in chemotherapy for colorectal cancer patients by regulating necroptosis. The findings in this study provide us a new target for interfere therapy in colorectal cancer.Key words: Colorectal cancer, miR-29b-3p, TRAF5, necroptosis, 5-fluorouracil resistance     

Serum-derived extracellular vesicles facilitate temozolomide resistance in glioblastoma through a HOTAIR-dependent mechanism

Extracellular vesicle (EV)-mediated transfer of long non-coding RNAs (lncRNAs) has been reported to regulate chemoresistance in various cancers. We herein investigate the therapeutic potential of bioinformatically identified HOTAIR transferred by serum-derived EVs (serum-EVs) in temozolomide (TMZ) resistance of glioblastoma (GBM) and the downstream mechanisms. EVs were isolated from the serum of GBM patients. Expression of HOTAIR was examined in the clinical tissue samples and serum-EVs of GBM patients. The downstream miRNAs of HOTAIR and its target genes were predicted in silico. The effects of the HOTAIR transmitted by serum-EVs in malignant phenotypes, tumor growth, and TMZ resistance were assessed in vitro and in vivo. HOTAIR expression was upregulated in clinical tissues, cells, and serum-EVs of GBM. Co-culture data showed that GBM-serum-EVs facilitated GBM cell proliferative and invasive phenotypes and TMZ resistance by elevating HOTAIR. In GBM cells, HOTAIR competitively bound to miR-526b-3p and weakened miR-526b-3p’s binding ability to EVA1, thus increasing the expression of EVA1. Furthermore, HOTAIR carried by serum-EVs promoted tumor growth and TMZ resistance in vivo by suppressing miR-526b-3p-mediated EVA1 inhibition. GBM-serum-EV-enclosed HOTAIR may augment GBM progression and chemoresistance through miR-526b-3p downregulation and EVA1 upregulation. These results provide a strategy to reduce TMZ resistance in GBM treatment.Subject terms: Neuroscience, Diseases     

Hsa_circ_0001495 contributes to cervical cancer progression by targeting miR-526b-3p/TMBIM6/mTOR axis

Cervical cancer (CC) is a common gynecological malignant tumor, causing poor survival rate. Circular RNAs (circRNAs) are abundantly expressed in CC with their stable loop structure. However, the underlying mechanism and biological function of circRNAs remained unclear. Using quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay, we measured the expression of hsa_circ_0001495, miR-526b-3p, and transmembrane Bax inhibitor motif containing 6 (TMBIM6) in CC tissues and cells. The relationship between miR-526b-3p and hsa_circ_0001495 or TMBIM6 was investigated by bioinformatics analysis, dual-luciferase and RIP analysis. Enzyme linked immunosorbent assay (ELISA) was conducted to evaluate glucose consumption and lactate production. 5-ethynyl-2′-deoxyuridine (EDU) assay were used to test cell proliferation. Cell apoptosis was analyzed by using flow cytometry assay. Transwell and wound-healing assays were used to measure cell invasion and migration. The expression of proteins was examined by western blot. Xenograft assay was applied to detect the effect of hsa_circ_0001495 in vivo. Our finding showed that hsa_circ_0001495 and TMBIM6 expression were upregulated, while miR-526b-3p was downregulated in CC tissues and cell lines. Hsa_circ_0001495 knockdown or TMBIM6 knockdown suppressed cell proliferation, migration, glycolysis, while promoted cell apoptosis in vitro, and hsa_circ_0001495 silence curbed tumor growth in vivo. Beside, hsa_circ_0001495 exerted its function in CC by positively regulating TMBIM6. Furthermore, hsa_circ_0001495 acted as a sponge for miR-526b-3p to regulate TMBIM6 expression. Hsa_circ_0001495/miR-526b-3p/TMBIM6 axis also regulated the phosphorylation of mammalian target of rapamycin (mTOR) in CC cells. In summary, hsa_circ_0001495 regulated the progression of CC by regulating miR-526b-3p/TMBIM6/mTOR pathway.     

MiR-27a-3p enhances the cisplatin sensitivity in hepatocellular carcinoma cells through inhibiting PI3K/Akt pathway

MicroRNAs (miRNAs) play an important role in drug resistance, and it is reported that miR-27a-3p regulated the sensitivity of cisplatin in breast cancer, lung cancer and ovarian cancer. However, the relationship between miR-27a-3p and chemosensitivity of cisplatin in hepatocellular carcinoma (HCC) was unclear, especially the underlying mechanism was unknown. In the present study, we analyzed miR-27a-3p expression levels in 372 tumor tissues and 49 adjacent tissues in HCC samples from TCGA database, and found that the miR-27a-3p was down-regulated in HCC tissues. The level of miR-27a-3p was associated with metastasis, Child–Pugh grade and race. MiR-27a-3p was regarded as a favorable prognosis indicator for HCC patients. Then, miR-27a-3p was overexpressed in HepG2 cell, and was knocked down in PLC cell. Next, we conducted a series of in vitro assays, including MTT, apoptosis and cell cycle assays to observe the biological changes. Further, inhibitor rate and apoptosis rate were detected with pre- and post-cisplatin treatment in HCC. The results showed that overexpression of miR-27a-3p repressed the cell viability, promoted apoptosis and increased the percentage of cells in G₀/G₁ phase. Importantly, overexpression of miR-27a-3p significantly increased the inhibitor rate and apoptosis rate with cisplatin intervention. Besides, we found that miR-27a-3p added cisplatin sensitivity potentially through regulating PI3K/Akt signaling pathway. Taken together, miR-27a-3p acted as a tumor suppressor gene in HCC cells, and it could be useful for modulating cisplatin sensitivity in chemotherapy.     

Inhibition of PTEN Gene Expression by Oncogenic miR-23b-3p in Renal Cancer

Background

miR-23b is located on chromosome number 9 and plays different roles in different organs especially with regards to cancer development. However, the functional significance of miR-23b-3p in renal cell carcinoma (RCC) has not been reported.

Methods and Results

We measured miR-23b-3p levels in 29 pairs of renal cell carcinoma and their normal matched tissues using real-time PCR. The expression level of miR-23b-3p was correlated with the 5 year survival rate of renal cancer patients. In 15 cases (52%), miR-23b-3p expression was found to be high. All patients with moderate to low miR-23b-3p expression survived 5 years, while those with high miR-23b-3p expression, only 50% survived. After knocking down miRNA-23b-3p expression in RCC cell lines, there was an induction of apoptosis and reduced invasive capabilities. MiR-23b-3p was shown to directly target PTEN gene through 3′UTR reporter assays. Inhibition of miR-23b-3p induces PTEN gene expression with a concomitant reduction in PI3-kinase, total Akt and IL-32. Immunohistochemistry showed the lack of PTEN protein expression in cancerous regions of tissue samples where the expression of miR-23b-3p was high. We studied the in vitro effects of the dietary chemo preventive agent genistein on miR-23b-3p expression and found that it inhibited expression of miR-23b-3p in RCC cell lines.

Conclusions

The current study shows that miR-23b-3p is an oncogenic miRNA and inhibits PTEN tumor suppressor gene in RCC. Therefore, inhibition of miR-23b-3p may be a useful therapeutic target for the treatment of renal cell carcinoma.     

miR-337-3p and its targets STAT3 and RAP1A modulate taxane sensitivity in non-small cell lung cancers

NSCLC (non-small cell lung cancer) often exhibits resistance to paclitaxel treatment. Identifying the elements regulating paclitaxel response will advance efforts to overcome such resistance in NSCLC therapy. Using in vitro approaches, we demonstrated that over-expression of the microRNA miR-337-3p sensitizes NCI-H1155 cells to paclitaxel, and that miR-337-3p mimic has a general effect on paclitaxel response in NSCLC cell lines, which may provide a novel adjuvant strategy to paclitaxel in the treatment of lung cancer. By combining in vitro and in silico approaches, we identified STAT3 and RAP1A as direct targets that mediate the effect of miR-337-3p on paclitaxel sensitivity. Further investigation showed that miR-337-3p mimic also sensitizes cells to docetaxel, another member of the taxane family, and that STAT3 levels are significantly correlated with taxane resistance in lung cancer cell lines, suggesting that endogenous STAT3 expression is a determinant of intrinsic taxane resistance in lung cancer. The identification of a miR-337-3p as a modulator of cellular response to taxanes, and STAT3 and RAP1A as regulatory targets which mediate that response, defines a novel regulatory pathway modulating paclitaxel sensitivity in lung cancer cells, which may provide novel adjuvant strategies along with paclitaxel in the treatment of lung cancer and may also provide biomarkers for predicting paclitaxel response in NSCLC.     

Circ_0000052/miR-382-3p axis induces PD-L1 expression and regulates cell proliferation and immune evasion in head and neck squamous cell carcinoma

A better understanding of the mechanisms underlying PD-L1 aberrant expression in head and neck squamous cell carcinoma (HNSCC) will help reveal predictive biomarkers and overcome resistance to treatment. In this study, the prognostic significance of PD-L1 in forty-five HNSCC archival samples was determined by qRT-PCR. The biological function associated with malignant behaviour was assessed by PD-L1 depletion, miR-382-3p re-expression and regulation of circ_0000052. The interactions of PD-L1-miRNA and miRNA-circRNA were determined by qRT-PCR, Western blot analysis, dual-luciferase reporter assays and RNA immunoprecipitation assays. PD-L1 was highly expressed in patient samples and cancer cell lines. Higher levels of PD-L1 were associated with patient recurrences and play a pivotal role in regulating cell proliferation, migration, invasion, clonogenicity and apoptosis. In addition to demonstrating that the IFN-γ/JAK2/STAT1 signalling pathway can induce PD-L1 overexpression in HNSCC, a novel mechanism by which upregulated circ_0000052 mediates PD-L1 overexpression was also demonstrated. To do this, circ_0000052 competitively binds to miR-382-3p and alleviates its repression of PD-L1. This leads to overexpression of PD-L1, causing the aggressiveness of the cells. Our data demonstrate that circ_0000052 is oncogenic, and the circ_0000052/miR-382-3p/PD-L1 axis is critical in HNSCC progression. The manipulation of circRNAs/miRNAs in combination with anti-PD-L1 therapy may improve personalized disease management.     

Ginsenoside Rb3 alleviates smoke-induced lung injury via the H19/miR-29b-3p/HGMB1/TLR4 signalling pathway

The over-activation of inflammation is involved in the pathogenesis of smoke-induced lung injury (SILI), while Rb3 treatment may alleviate smoke-induced lung injury by down-regulating the expression of H19, a regulator of miR-29b expression. Moreover, HMGB1 is an important mediator of inflammation. Therefore, in this study, we set up an animal model of SILI and treated it with Rb3 to study the effect of Rb3 on the treatment of SILI and the involvement of H19/miR-29b/HMGB1/TLR4 signalling. SILI mice treated with Rb3 before H&E staining and TUNEL assay were conducted to observe the pathological damages and status of apoptosis in each group. Real-time PCR, Western blot, computational analysis and luciferase assays were utilized to establish the signalling pathway involved in the pathogenesis of SILI and the action of Rb3 treatment. Rb3 treatment alleviated pathological changes in the lungs while decreasing the levels of W/D ratio and cell apoptotic index. H19 was validated to sponge miR-29b-3p, while HMGB1 mRNA was validated to be a target gene of miR-29b-3. As a result, a signalling pathway of H19/miR-29b-3p/HMGB1 was established. Cell viability was evidently reduced after 72 hours of treatment with CSE, but the treatment of Rb3 elevated the expression of H19 and HMBG1 in the presence of CSE. Also, CSE-induced inhibition of miR-29b-3p expression was restored by Rb3. The findings of this study collectively demonstrated that Rb3 exhibited its therapeutic effect during the treatment of SILI via modulating the H19/miR-29b-3p/HMBG1 signalling pathway.     

Circular RNA circ_103820 suppresses lung cancer tumorigenesis by sponging miR-200b-3p to release LATS2 and SOCS6

A growing number of circular RNAs (circRNAs) have been identified and verified in several cancers. However, highly efficient therapeutic methods based on circRNAs in lung cancer remain largely unexplored. In the present study, we identified a novel circular RNA, hsa_circ_103820, based on Gene Expression Omnibus (GEO) data. Functionally, overexpression of hsa_circ_103820 showed significant inhibitory effects on the proliferation, migration and invasion of lung cancer cells, and knockdown of hsa_circ_103820 played promoting roles. Regarding the mechanism, we revealed that miR-200b-3p was a direct target of hsa_circ_103820 and that LATS2 and SOCS6 were the downstream target genes of miR-200b-3p. Therefore, we identified a novel potential tumor suppressive function of hsa_circ_103820 in lung cancer.Subject terms: RNA, Non-small-cell lung cancer     

MORC4 is a novel breast cancer oncogene regulated by miR-193b-3p

A better understanding of breast cancer pathogenesis would contribute to improved diagnosis and therapy and potentially decreased mortality rates. Here, we found that the MORC family CW-type zinc finger 4 (MORC4) overexpression in breast cancer tissues is associated with poor survival, and the short-interfering RNA knockdown of MORC4 suppresses the growth of breast cancer cells by promoting apoptosis. To investigate the mechanisms associated with MORC4 upregulation, microRNAs potentially targeting MORC4 were analyzed, with miR-193b-3p identified as the regulator and a negative correlation between miR-193b-3p and MORC4 expression determined in both breast cancer cell lines and tissues. Further analysis verified that MORC4 silencing did not affect miR-193b-3p expression, although altered miR-193b-3p expression attenuated MORC4 protein levels. Moreover, dual-luciferase reporter assays verified miR-193b-3p binding to the 3′ untranslated region of MORC4. Furthermore, restoration of miR-193b-3p expression in breast cancer cells led to decreased growth and activation of apoptosis, which was consistent with results associated with MORC4 silencing in breast cancer cells. These results identified MORC4 as differentially expressed in breast cancer cells and tissues and its downregulation by miR-193b-3p, as well as its roles in regulating the growth of breast cancer cells via regulation of apoptosis. Our findings offer novel insights into potential mechanisms associated with breast cancer pathogenesis.     

Methylation of miR-19b-3p promoter exacerbates inflammatory responses in sepsis-induced ALI via targeting KLF7

Sepsis-induced acute lung injury is associated with dysregulated inflammatory reactions. MiR-19b-3p level was reported to be downregulated in patients with sepsis. To evaluate the role of miR-19b-3p in sepsis, cecum ligation and puncture-induced mouse sepsis model and lpopolysaccharide (LPS)-treated pulmonary microvascular endothelial cells (PMVECs) were used. For in vivo study, lung tissue was harvested for hematoxylin and eosin (H&E) staining, tumor necrosis factor-α, interleukin-6 (IL-6), IL-1β, and p-p65, p-IκB measuring. Cell apoptosis was assessed by TUNEL assay. For in vitro study, cell proliferation and apoptosis were detected by CCK-8 and flow cytometry, respectively. Methylation of miR-19b-3p promoter was measured by methylation-specific PCR (MSP) assay. The target of miR-19b-3p was determined by dual-luciferase reporter gene assay. The level of miR-19b-3p was determined to be downregulated in vitro and in vivo. In addition, miR-19b-3p protected mice from inflammation injury through inhibiting NF-κB signaling pathway. Overexpression of miR-19b-3p increased cell viability, decreased apoptosis, and proinflammatory cytokines secretion in LPS-treated PMVECs. Besides these, Krüppel-like factor 7 (KLF7) was confirmed as the target of miR-19b-3p. And methylation of miR-19b-3p was the reason of decreased miR-19b-3p level. In conclusion, miR-19b-3p protected cells from sepsis-induced inflammation injury via inhibiting NF-κB signaling pathway, and KLF7 was a potential target.     

Decreased miR-30b-5p expression by DNMT1 methylation regulation involved in gastric cancer metastasis

miRNAs have emerged as crucial regulators in the regulation of development as well as human diseases, especially tumorigenesis. The aims of this study are to evaluate miR-30b-5p expression pattern and mechanism in gastric carcinogenesis due to which remains to be determined. Expression of miR-30b-5p was analyzed in 51 gastric cancer cases and 4 cell lines by qRT-PCR. The effect of DNA methylation on miR-30b-5p expression was assessed by MSP and BGS. In order to know whether DNMT1 increased miR-30b-5p promoter methylation, DNMT1 was depleted in cell lines AGS and BGC-823. The role of miR-30b-5p on cell migration was evaluated by wound healing assays. Decreased expression of miR-30b-5p was found in gastric cancer samples. In tumor, the expression level of miR-30b-5p was profound correlated with lymph node metastasis (P = 0.019). The level of miR-30b-5p may be restored by DNA demethylation and DNMT1 induced miR-30b-5p promoter methylation. In vitro functional assays implied that enforced miR-30b-5p expression affected cell migration, consistent with tissues analysis. Our findings uncovered that miR-30b-5p is significantly diminished in gastric cancer tissues, providing the first insight into the epigenetic mechanism of miR-30b-5p down-regulation, induced by DNMT1, and the role of miR-30b-5p in gastric cancer carcinogenesis. Overexpression of miR-30b-5p inhibited cell migration. Thus, miR-30b-5p may represent a potential therapeutic target for gastric cancer therapy.     

Inhibition of miR-130b-3p restores autophagy and attenuates intervertebral disc degeneration through mediating ATG14 and PRKAA1

Oxidative stress-induced autophagy dysfunction is involved in the pathogenesis of intervertebral disc degeneration (IVDD). MicroRNAs (miRNAs) not only have been regarded as important regulators of IVDD but also reported to be related to autophagy. This research was aimed to explore the role of miR-130b-3p in IVDD and its regulation on autophagy mechanism. The miR-130b-3p expression in the patient’s degenerative nucleus pulposus (NP) samples and rat NP tissues was detected by qRT-PCR and FISH assay. The miR-130b-3p was knocked down or overexpressed in the human NP cells by lentivirus transfection. TBHP was used to induce oxidative stress in the human NP cells. Apoptosis, senescence, and autophagy were evaluated by flow cytometry, β-gal staining, immunofluorescence, electron microscopy, and Western blot in the miR-130b-3p knocked down human NP cells under TBHP treatment. The relationship between the miR-130b-3p and ATG14 or PRKAA1 was confirmed by luciferase assay. The siRNA transfection was used to knock down the ATG14 and PRKAA1 expression, and then the human NP cells functions were further determined. In the in vivo experiment, the IVDD rat model was constructed and an adeno-associated virus (AAV)-miR-130b-3p inhibitor was intradiscally injected. After that, MRI and histological staining were conducted to evaluate the role of miR-130b-3p inhibition in the IVDD rat model. We found that the miR-130b-3p was upregulated in the degenerative NP samples from humans and rats. Interestingly, the inhibition of miR-130b-3p rescued oxidative stress-induced dysfunction of the human NP cells, and miR-130b-3p inhibition upregulated autophagy. Mechanistically, we confirmed that the miR-130b-3p regulated the ATG14 and PRKAA1 directly and the knockdown of the ATG14 or PRKAA1 as well as the treatment of autophagy inhibitor blockaded the autophagic flux and reversed the protective effects of miR-130b-3p inhibition in the TBHP-induced human NP cells. Furthermore, the inhibition of the miR-130b-3p via AAV- miR-130b-3p injection ameliorated the IVDD in a rat model. These data demonstrated that the miR-130b-3p inhibition could upregulate the autophagic flux and alleviate the IVDD via targeting ATG14 and PRKAA1.

The translational potential of this article: The suppression of miR-130b-3p may become an effective therapeutic strategy for IVDD.

     

LncRNA-ATB regulates epithelial-mesenchymal transition progression in pulmonary fibrosis via sponging miR-29b-2-5p and miR-34c-3p

Dysregulation of non-coding RNAs (ncRNAs) has been proved to play pivotal roles in epithelial-mesenchymal transition (EMT) and fibrosis. We have previously demonstrated the crucial function of long non-coding RNA (lncRNA) ATB in silica-induced pulmonary fibrosis-related EMT progression. However, the underlying molecular mechanism has not been fully elucidated. Here, we verified miR-29b-2-5p and miR-34c-3p as two vital downstream targets of lncRNA-ATB. As opposed to lncRNA-ATB, a significant reduction of both miR-29b-2-5p and miR-34c-3p was observed in lung epithelial cells treated with TGF-β1 and a murine silicosis model. Overexpression miR-29b-2-5p or miR-34c-3p inhibited EMT process and abrogated the pro-fibrotic effects of lncRNA-ATB in vitro. Further, the ectopic expression of miR-29b-2-5p and miR-34c-3p with chemotherapy attenuated silica-induced pulmonary fibrosis in vivo. Mechanistically, TGF-β1-induced lncRNA-ATB accelerated EMT as a sponge of miR-29b-2-5p and miR-34c-3p and shared miRNA response elements with MEKK2 and NOTCH2, thus relieving these two molecules from miRNA-mediated translational repression. Interestingly, the co-transfection of miR-29b-2-5p and miR-34c-3p showed a synergistic suppression effect on EMT in vitro. Furthermore, the co-expression of these two miRNAs by using adeno-associated virus (AAV) better alleviated silica-induced fibrogenesis than single miRNA. Approaches aiming at lncRNA-ATB and its downstream effectors may represent new effective therapeutic strategies in pulmonary fibrosis.     

MicroRNA-217 Functions as a Tumour Suppressor Gene and Correlates with Cell Resistance to Cisplatin in Lung Cancer

MiR-217 can function as an oncogene or a tumour suppressor gene depending on cell type. However, the function of miR-217 in lung cancer remains unclear to date. This study aims to evaluate the function of miR-217 in lung cancer and investigate its effect on the sensitivity of lung cancer cells to cisplatin. The expression of miR-217 was detected in 100 patients by real-time PCR. The effects of miR-217 overexpression on the proliferation, apoptosis, migration and invasion of SPC-A-1 and A549 cells were investigated. The target gene of miR-217 was predicted by Targetscan online software, screened by dual luciferase reporter gene assay and demonstrated by Western blot. Finally, the effects of miR-217 up-regulation on the sensitivity of A549 cells to cisplatin were determined. The expression of miR-217 was significantly lower in lung cancer tissues than in noncancerous tissues (p < 0.001). The overexpression of miR-217 significantly inhibited the proliferation, migration and invasion as well as promoted the apoptosis of lung cancer cells by targeting KRAS. The up-regulation of miR-217 enhanced the sensitivity of SPC-A-1 and A549 cells to cisplatin. In conclusion, miR-217 suppresses tumour development in lung cancer by targeting KRAS and enhances cell sensitivity to cisplatin. Our results encourage researchers to use cisplatin in combination with miR-217 to treat lung cancer. This regime might lead to low-dose cisplatin application and cisplatin side-effect reduction.