Multidrug resistance (MDR) is common in patients and has been linked to transforming growth factor‐β1 (TGF‐β1) and overexpression of drug efflux transporters P‐glycoprotein (P‐gp) and breast cancer resistance protein (BCRP), although the molecular mechanisms remain largely unknown. This study aimed to investigate the mechanisms underlying TGF‐β1‐induced MDR in hepatocellular carcinoma (HCC) cells. It was found that TGF‐β1 upregulated HOX transcript antisense RNA (HOTAIR) expression in HCC cells. When drosophila mothers against decapentaplegic 4 (SMAD4) was silenced, HOTAIR expression was accordingly reduced. Meanwhile, miR‐145 expression was increased in the case HOTAIR was silenced. If the enhancer of zeste homolog 2 (EZH2) was knocked down using small interfering RNA (siRNA), miR‐145 expression was decreased. Then, the regulatory role of miR‐145 in P‐gp and BCRP expression was explored. The results showed that the expression of P‐gp and BCRP protein was suppressed by miR‐145 through binding to the 3′‐untranslated regions (3′‐UTRs) of P‐gp and BCRP. In conclusion, our study revealed a novel mechanism explaining TGF‐β1‐induced MDR in HCC through upregulating P‐gp and BCRP via the SMAD4/HOTAIR/miR‐145 axis.

Src homology 2 domain-containing protein tyrosine phosphatase (SHP2) is a non-receptor protein tyrosine phosphatase encoded by the Ptpn11 gene, which regulates cell growth, differentiation and apoptosis via modulating various signaling...

MicroRNAs (miRNAs) are a class of endogenous non-coding single-stranded small-molecule RNAs that regulate gene expression by repressing target messenger RNA (mRNA) translation or degrading mRNA. miR-34a is one of the most important miRNAs participating in various physiological and pathological processes. miR-34a is abnormally expressed in a variety of tumors. The roles of miR-34a in gastrointestinal cancer (GIC) draw lots of attention. Numerous studies have demonstrated that dysregulated miR-34a is closely related to the proliferation, differentiation, migration, and invasion of tumor cells, as well as the diagnosis, prognosis, treatment, and chemo-resistance of tumors. Thus, we systematically reviewed the abnormal expression and regulatory roles of miR-34a in GICs including esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), hepatocellular carcinoma (HCC), pancreatic cancer (PC), and gallbladder cancer (GBC). It may provide a profile of versatile roles of miR-34a in GICs.

The single nucleotide polymorphisms (SNPs) in the microRNA precursor (pre-miRNA) may modulate the posttranscriptional regulation of gene expression and explain individual sensitivity to chemotherapy. Here we investigated the correlation between 23 SNPs in the pre-miRNA and the efficacy of capecitabine-based chemotherapy in 274 advanced colon cancer patients. Statistical analysis indicated that much more patients with rs744591 A/C(48.03%), C/C (53.45%) or C allele (49.73%) responded to the chemotherapy than those with the A/A genotype (33.71%). The response rates of rs745666 G/C heterozygous patients (35.25%) and C allele carriers (39.69%) were apparently less than that of the G/G homozygous patients (56.25%). Moreover, three SNPs rs2114358, rs35770269, and rs73239138 were significantly associated with the occurrence of side effects of chemotherapy. The patients with rs2114358 C allele (OR = 2.016) or rs35770269 T allele (OR = 2.299) were much more prone to endure adverse events. However, the incidence of side effect was lower in the patients carrying rs73239138 A allele than those with G/G genotype (OR = 0.500). Our findings demonstrate that genetic variations in pre-miRNA may influence the efficacy of capecitabine-based chemotherapy in advanced colon cancer patients.

No abstract