m6A modification of lncRNA PHKA1-AS1 enhances Actinin Alpha 4 stability and promotes non-small cell lung cancer metastasis.

Cancer is a disease with molecular heterogeneity that is closely related to gene mutations and epigenetic changes. The principal histological subtype of lung cancer is non-small cell lung cancer (NSCLC). Long noncoding RNA (lncRNA) is a kind of RNA that is without protein coding function, playing a critical role in the progression of cancer. In this research, the regulatory mechanisms of lncRNA phosphorylase kinase regulatory subunit alpha 1 antisense RNA 1 (PHKA1-AS1) in the progression of NSCLC were explored. The increased level of N6-methyladenosine (m6A) modification in NSCLC caused the high expression of PHKA1-AS1. Subsequently, high-expressed PHKA1-AS1 significantly facilitated the proliferation and metastasis of NSCLC cells, and these effects could be reversed upon the inhibition of PHKA1-AS1 expression, both in vivo and in vitro. Additionally, the target protein of PHKA1-AS1 was actinin alpha 4 (ACTN4), which is known as an oncogene. Herein, PHKA1-AS1 could enhance the protein stability of ACTN4 by inhibiting its ubiquitination degradation process, thus exerting the function of ACTN4 in promoting the progress of NSCLC. In conclusion, this research provided a theoretical basis for further exploring the potential mechanism of NSCLC metastasis and searching novel biomarkers related to the pathogenesis and progression of NSCLC.

Jaceosidin inhibits the progression and metastasis of NSCLC by regulating miR-34c-3p/Integrin α2ß1 axis.

Non-coding RNAs are crucial for cancer progression, among which miR-34c-3p has been demonstrated to be a tumor suppressor in non-small cell lung cancer (NSCLC). In this study, we attempt to identify flavonoids that can up-regulate miR-34c-3p expression, evaluate the anticancer activity of the flavonoids and explore its underlying mechanism in NSCLC cells. Six flavonoids were screened by RT-qPCR and we found that jaceosidin significantly increased miR-34c-3p expression in A549 cells. We found that jaceosidin inhibited the proliferation, migration and invasion of A549 and H1975 cells in a dose-relevant manner, indicated by cell counting kit (CCK-8) assay, wound healing assay, transwell assay and EdU assay, we observed that jaceosidin inhibited the proliferation, migration and invasion of A549 and H1975 cells in a dose-relevant manner. Further research suggested that miR-34c-3p bound to the transcriptome of integrin α2ß1 and then inhibited its expression, leading to the inhibitory effect on the migration and invasion of NSCLC. Our study sheds some light on anti-tumor of jaceosidin and provides a potential lead compound for NSCLC therapy.

Research Progress on Natural Diterpenoids in Reversing Multidrug Resistance.

Multidrug resistance (MDR) is one of the main impediments in successful chemotherapy in cancer treatment. Overexpression of ATP-binding cassette (ABC) transporter proteins is one of the most important mechanisms of MDR. Natural products have their unique advantages in reversing MDR, among which diterpenoids have attracted great attention of the researchers around the world. This review article summarizes and discusses the research progress on diterpenoids in reversing MDR.

[Expression and Clinical Significance of Serum MiR-424 and MiR-765 in Multiple Myeloma].

OBJECTIVE: To investigate the expression and clinical significance of miR-424 and miR-765 in patients with multiple myeloma (MM). METHODS: The eighty-one MM patients admitted to Sanya Central Hospital from January 2017 to July 2020 were divided into phase Ⅰ (n=16), phase Ⅱ (n=25) and phase Ⅲ (n=40) according to the international staging system, while they were divided into IgG type (n=46), IgA type (n=19), light chain type (n=10) and non secretory type (n=6) according to the results of immunotyping. Another 50 healthy normal persons in the same period were selected as the control group. The levels of serum miR-424, miR-765 and Cystatin C (Cys-C) were measured in each group. The diagnostic value of serum miR-424, miR-765 and Cys-C in MM was estimated by ROC curve. Pearson correlation was used to analyze the correlation between serum levels of miR-424, miR-765 and Cys-C in MM patients. RESULTS: The serum levels of miR-424 (2.74±1.30 vs 0.85±0.26), miR-765 (2.05±0.82 vs 0.63±0.17) and Cys-C ï¼»(2.18±0.86 vs 0.72±0.15) mg/Lï¼½ in MM group were significantly higher than those in control group (P<0.001). The serum levels of miR-424 (5.08±2.36 vs 1.12±0.34, 2.24±0.93), miR-765 (3.50±1.52 vs 0.74±0.20, 1.78±0.65) and Cys-C ï¼»(3.81±1.30 vs 0.92±0.24, 1.68±0.55) mg/Lï¼½ in MM patients at stage Ⅲ were significantly higher than those in patients at stage Ⅰ and Ⅱ (P<0.001). Also the serum levels of the three molecules in phase II were significantly higher than those in phase I (P<0.001). The serum levels of miR-424 and miR-765 in MM patients at IgG type were significantly higher than those at IgA, light chain and non secretory types (P<0.001). ROC curve analysis showed that the area under the curve (0.952，95%CI: 0.890-0.993) was greatest for the combination of miR-424, miR-765 and Cys-C for diagnosis of MM, and its sensitivity and specificity were 95.0% and 87.2%. The results of correlation analysis showed that the serum levels of miR-424 and miR-765 were positively correlated with Cys-C (r=0.795，r=0.760). CONCLUSION: The serum levels of miR-424 and miR-765 in MM patients are significantly increased in the pattern increasing with the progression of MM stage. Combined with Cys-C, miR-424 and miR-765 have high value in the diagnosis of MM.

Application of microfluidic chips in anticancer drug screening.

With the continuous development of drug screening technology, new screening methodologies and technologies are constantly emerging, driving drug screening into rapid, efficient and high-throughput development. Microfluidics is a rising star in the development of innovative approaches in drug discovery. In this article, we summarize the recent years' progress of microfluidic chip technology in drug screening, including the developmental history, structural design, and applications in different aspects of microfluidic chips on drug screening. Herein, the existing microfluidic chip screening platforms are summarized from four aspects: chip structure design, sample injection and drive system, cell culture technology on a chip, and efficient remote detection technology. Furthermore, this review discusses the application and developmental prospects of using microfluidic chips in drug screening, particularly in screening natural product anticancer drugs based on chemical properties, pharmacological effects, and drug cytotoxicity.

[Expression and Clinical Significance of MiR-146a and MiR-221 in Childhood Acute T Lymphoblastic Leukemia].

OBJECTIVE: To investigate the expression of miR-146a and miR-211 in peripheral blood mononuclear cells (PBMNC) of children with acute T-lymphoblastic leukemia (T-ALL) and their clinical significance. METHODS: One hundred and thirty newly diagnosed children with T-ALL from Hainan Third People's Hospital (T-ALL group) and 50 healthy persons (control group) were selected. The newly diagnosed T-ALL patients before treatment were taken as initial group, the patients reachived complete remission after induction therapy for 33 days were taken as remission group (n=98), the patients not reachived complete remission after induction therapy fore 33 days were taken as rafractory group (n=32). The expression levels of miR-146a and miR-221 in PBMNC were detected by real-time fluorescence quantitative PCR. ROC curve analysis was used to evaluate the diagnostic value of miR-146a and miR-221 for T-ALL, Pearson correlation analysis was used to estimate the correlation of miR-146a and miR-221 expression with white blood cell count in children with T-ALL. RESULTS: The expression levels of miR-146a and miR-221 of PBMNC in T-ALL group were significantly higher than those in control group (5.83±1.54 vs 0.96±0.17) (7.13±2.60 vs 1.64±0.51) (P＜0.01). The expression levels of miR-146a and miR-221 in refractory group were significantly higher than those in remission group and initial group (8.74±2.35 vs 1.70±0.63 and 5.83±1.54) (11.316±4.83 vs 2.62±0.85 and 7.13±2.60) (P＜0.01). The expression levels of miR-146a and miR-221 correlated with white blood cell count, risk typing and MRD (P＜0.05). ROC curve analysis showed that the best cutoff values of miR-146a and miR-221 for diagnosing childhood T-ALL were 3.90 and 5.28, resoectively. While the AUC (95% CI) of the T-ALL jointy diagnosed by miR-146a and miR-221 was 0.835 (0.764-0.892), and it's sensitivity and specificity were 85.0% and 77.2%, respectively. The correlation analysis showed that the expression levels of miR-146a and miR-221 in PBMNC of children with T-ALL positively correlated with the white blood cell count (r=0.705, r=0.653, P＜0.01), and that of miR-146a positively correlated with miR-221 (r=0.784, P＜0.01). CONCLUSION: The expression of miR-146a and miR-221 is up-regulated in children with T-ALL and closely relates with the prognosis of children with T-ALL. The combined detection of miR-146a and miR-221 is certain value for diagnosis of T-ALL.