LncRNA RPL29P2 promotes peritoneal fibrosis and impairs peritoneal transport function via miR-1184 in peritoneal dialysis.

Peritoneal dialysis (PD), hemodialysis and kidney transplantation are the three therapies to treat uremia. However, PD is discontinued for peritoneal membrane fibrosis (PMF) and loss of peritoneal transport function (PTF) due to damage from high concentrations of glucose in PD fluids (PDFs). The mechanism behind PMF is unclear, and there are no available biomarkers for the evaluation of PMF and PTF. Using microarray screening, we found that a new long noncoding RNA (lncRNA), RPL29P2, was upregulated in the PM (peritoneal membrane) of long-term PD patients, and its expression level was correlated with PMF severity and the PTF loss. In vitro and rat model assays suggested that lncRNA RPL29P2 targets miR-1184 and induces the expression of collagen type I alpha 1 chain (COL1A1). Silencing RPL29P2 in the PD rat model might suppress the HG-induced phenotypic transition of Human peritoneal mesothelial cells (HPMCs), alleviate HG-induced fibrosis and prevent the loss of PTF. Overall, our findings revealed that lncRNA RPL29P2, which targets miR-1184 and collagen, may represent a useful marker and therapeutic target of PMF in PD patients.

Effects of Dietary Supplementation with Tea Residue on Growth Performance, Digestibility, and Diarrhea in Piglets.

Thirty-six healthy 21-day-old weaned ternary piglets (Duroc × Landrace × Yorkshire) were randomly divided into two treatments with 18 replicates per treatment and one pig per replicate. The control group was fed with a basal diet and the test group was fed with diets supplemented with 1 kg/t tea residue. The test period was 28 days. The results are as follows: The addition of tea residue in the diet had no significant effect on the growth performance of weaned piglets (p > 0.05), but it could significantly reduce the diarrhea rate of piglets from 1 to 7 days and 1 to 28 days (p < 0.05). Compared with the control group, the dietary supplementation of tea residue had no significant effect on nutrient apparent digestibility, plasma biochemical indexes and plasma immune indexes (p > 0.05) but increased the content of glutathione in plasma (p < 0.05). Tea residue had no significant effect on the morphology of the jejunum and ileum of piglets (p > 0.05), but it could significantly reduce the content of chloride ions in feces (p < 0.05). Compared with the basal diet group, there was no significant difference in the relative expression of TMEM16A and CFTR mRNA in the colon of weaned piglets (p > 0.05). The whole-cell patch clamp recording showed that the TMEM16A and CFTR ion channels could be activated by ionomycin and forskolin, respectively. However, when HT-29 cells transfected with TMEM16A and CFTR channels were treated with tea residue extract, it could significantly inhibit the chloride current of the TMEM16A and CFTR ion channels (p < 0.05).

Structural characterization of lignin from the green pretreatments for co-producing xylo-oligosaccharides and glucose: Toward full biomass utilization.

Three green non-enzymatic catalysis pretreatments (NECPs) including autohydrolysis, subcritical CO2-assisted seawater autohydrolysis, and inorganic salt catalysis were utilized to simultaneously produce xylo-oligosaccharides (XOS), glucose, and cellulolytic enzyme lignin (CEL) from sugarcane bagasse (SCB). The yield of XOS in all three NECPs was over 50 % with a competitive glucose yield of enzymatic hydrolysis. And the effects of different pretreatments on the chemical structure and composition of CEL samples were also investigated. The pretreatments significantly increased the thermal stability, yield, and purity of the CEL samples. Moreover, the net yield of lignin was 58.3 % with lignin purity was 98.9 % in the autohydrolysis system. Furthermore, there was a decrease in the molecular weight of CEL samples as the pretreatment intensity increased. And the original lignin structural units sustained less damage during the NECPs, due to the cleavage of the ß-O-4 bonds dominating lignin degradation. Meanwhile, these pretreatments increased the phenolic-OH in CEL samples, making the lignin more reactive, and enhancing its subsequent modification and utilization. Collectively, the described techniques have demonstrated practical significance for the coproduction of XOS and glucose, and lignin, providing a promising strategy for full utilization of biomass.

Malnutrition and cerebral intraparenchymal damage in patients with thrombosis of dural sinuses and/or cerebral veins.

BACKGROUNDS: Thrombosis of dural sinuses and/or cerebral veins (CVT) is an uncommon form of cerebrovascular disease. Malnutrition is common in patients with cerebrovascular disease, and early assessment of malnutrition and individualized nutritional treatment have been reported to improve functional outcomes of these patients. As for CVT patients, little is known about whether these patients would suffer from malnutrition. Also, the correlation between malnutrition and cerebral intraparenchymal damage (CID) in CVT patients was rarely studied. METHODS: Patients with CVT were retrospectively included in this observational study. Multivariate logistic regressions were used to investigate the effects of nutritional indexes on the risk of CID. Subsequently, we used the independent risk factors to construct the nomogram model, and the consistency index (C-index), calibration curve and decision curve analysis (DCA) to assess the reliability and applicability of the model. RESULTS: A total of 165 patients were included in the final analysis. Approximately 72.7% of CVT patients were regarded as malnourished by our malnutrition screening tools, and malnutrition is associated with an increased risk of CID. Prognostic Nutritional Index (PNI) (OR = 0.873; CI: 0.791, 0.963, p = 0.007) remained as an independent predictor for CID after adjustment for other risk factors. The nomogram model showed that PNI and gender have a great contribution to prediction. Besides, the nomogram model was consistent with the actual observations of CID risk (C-index = 0.65) and was of clinical significance. CONCLUSIONS: We reported that malnutrition, as indicated by PNI, was associated with a higher incidence of CID in CVT patients. Also, we have constructed a nomogram for predicting the risk of CID in these patients.

The subacute toxicity and underlying mechanisms of biomimetic mesoporous polydopamine nanoparticles.

Recently, mesoporous nanomaterials with widespread applications have attracted great interest in the field of drug delivery due to their unique structure and good physiochemical properties. As a biomimetic nanomaterial, mesoporous polydopamine (MPDA) possesses both a superior nature and good compatibility, endowing it with good clinical transformation prospects compared with other inorganic mesoporous nanocarriers. However, the subacute toxicity and underlying mechanisms of biomimetic mesoporous polydopamine nanoparticles remain uncertain. Herein, we prepared MPDAs by a soft template method and evaluated their primary physiochemical properties and metabolite toxicity, as well as potential mechanisms. The results demonstrated that MPDA injection at low (3.61 mg/kg) and medium doses (10.87 mg/kg) did not significantly change the body weight, organ index or routine blood parameters. In contrast, high-dose MPDA injection (78.57 mg/kg) is associated with disturbances in the gut microbiota, activation of inflammatory pathways through the abnormal metabolism of bile acids and unsaturated fatty acids, and potential oxidative stress injury. In sum, the MPDA dose applied should be controlled during the treatment. This study first provides a systematic evaluation of metabolite toxicity and related mechanisms for MPDA-based nanoparticles, filling the gap between their research and clinical transformation as a drug delivery nanoplatform.

Collagen changes in rabbit conjunctiva after conjunctival crosslinking.

This study aims to determine the ultrastructural changes in collagen fibrils in rabbit conjunctiva after conjunctival crosslinking using riboflavin and ultraviolet A (UVA) light at an irradiation intensity of 45 mW/cm2. Conjunctival crosslinking may increase conjunctival stiffness. The supertemporal quadrants of the right eyes of 24 adult rabbits were treated with a topical riboflavin solution (0.25%) before irradiation with UVA light at 45 mW/cm2 for 4 min. After 3 weeks, the collagen fibrils in fibril bundles were examined by electron microscopy. Immunohistochemical staining was used to detect the expression levels of collagen I and collagen III in the rabbits' conjunctiva. The diameter of the collagen fibrils in the fibril bundles varied slightly, ranging from 30 to 60 nm in the conjunctival stroma of the control group. In the treatment group, the diameter of collagen fibrils ranged from 60 to 90 nm. The thickest collagen fibrils were observed in the treatment group (up to 90 nm in diameter). In contrast, those in the conjunctival stroma of the control group were considerably smaller (up to 60 nm in diameter). However, thicknesses of collagen fibrils displayed a unimodal distribution. Both collagen I and collagen III increased after treatment with riboflavin and UVA light irradiation at 45 mW/cm2. The data indicate that in rabbits, conjunctival crosslinking with riboflavin and UVA light at 45 mW/cm2 for 4 min is safe and does not induce ultrastructural alterations of the conjunctival cells. The conjunctival crosslinking with riboflavin and UVA light at 45 mW/cm2 can increase the diameter of collagen fibrils, but the average densities of collagen I and collagen III have no statistical significance.

Dynamic structural evolution of lignin macromolecules and hemicelluloses during Chinese pine growth.

To comprehend the biosynthesis processes of conifers, it is essential to investigate the disparity between the cell wall shape and the interior chemical structures of polymers throughout the development of Chinese pine. In this study, branches of mature Chinese pine were separated according to their growth time (2, 4, 6, 8 and 10 years). The variation of cell wall morphology and lignin distribution was comprehensively monitored by scanning electron microscopy (SEM) and confocal Raman microscopy (CRM), respectively. Moreover, the chemical structures of lignin and alkali-extracted hemicelluloses were extensively characterized by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The thickness of latewood cell walls increased steadily from 1.29 µm to 3.38 µm, and the structure of the cell wall components became more complicated as the growth time increased. Based on the structural analysis, it was found that the content of ß-O-4 (39.88-45.44/100 Ar), ß-ß (3.20-10.02/100 Ar) and ß-5 (8.09-15.35/100 Ar) linkages as well as the degree of polymerization of lignin increased with the growth time. The complication propensity increased significantly over 6 years before slowing to a trickle over 8 and 10 years. Furthermore, alkali-extracted hemicelluloses of Chinese pine mainly consist of galactoglucomannans and arabinoglucuronxylan, in which the relative content of galactoglucomannans increased with the growth of the pine, especially from 6 to 10 years.

Using patient-derived organoids to predict locally advanced or metastatic lung cancer tumor response: A real-world study.

Predicting the clinical response to chemotherapeutic or targeted treatment in patients with locally advanced or metastatic lung cancer requires an accurate and affordable tool. Tumor organoids are a potential approach in precision medicine for predicting the clinical response to treatment. However, their clinical application in lung cancer has rarely been reported because of the difficulty in generating pure tumor organoids. In this study, we have generated 214 cancer organoids from 107 patients, of which 212 are lung cancer organoids (LCOs), primarily derived from malignant serous effusions. LCO-based drug sensitivity tests (LCO-DSTs) for chemotherapy and targeted therapy have been performed in a real-world study to predict the clinical response to the respective treatment. LCO-DSTs accurately predict the clinical response to treatment in this cohort of patients with advanced lung cancer. In conclusion, LCO-DST is a promising precision medicine tool in treating of advanced lung cancer.

The design of small-molecule prodrugs and activatable phototherapeutics for cancer therapy.

Cancer remains as one of the most significant health problems, with approximately 19 million people diagnosed worldwide each year. Chemotherapy is a routinely used method to treat cancer patients. However, current treatment options lack the appropriate selectivity for cancer cells, are prone to resistance mechanisms, and are plagued with dose-limiting toxicities. As such, researchers have devoted their attention to developing prodrug-based strategies that have the potential to overcome these limitations. This tutorial review highlights recently developed prodrug strategies for cancer therapy. Prodrug examples that provide an integrated diagnostic (fluorescent, photoacoustic, and magnetic resonance imaging) response, which are referred to as theranostics, are also discussed. Owing to the non-invasive nature of light (and X-rays), we have discussed external excitation prodrug strategies as well as examples of activatable photosensitizers that enhance the precision of photodynamic therapy/photothermal therapy. Activatable photosensitizers/photothermal agents can be seen as analogous to prodrugs, with their phototherapeutic properties at a specific wavelength activated in the presence of disease-related biomarkers. We discuss each design strategy and illustrate the importance of targeting biomarkers specific to the tumour microenvironment and biomarkers that are known to be overexpressed within cancer cells. Moreover, we discuss the advantages of each approach and highlight their inherent limitations. We hope in doing so, the reader will appreciate the current challenges and available opportunities in the field and inspire subsequent generations to pursue this crucial area of cancer research.

Structure regulated 3D flower-like lignin-based anode material for lithium-ion batteries and its storage kinetics.

As a green sustainable material, lignin-derived porous carbon (LPC) exhibits great application potential when used as the anode material in lithium-ion batteries (LIBs), but the applications are limited by the heterogeneity of the lignin precursor. Therefore, it is crucial to reveal the relationship among lignin properties, porous carbon structure and the kinetics of lithium-ion storage. Herein, LPCs from fractionated lignin have been prepared by an eco-friendly and recyclable activator. The structure of the LPCs was regulated by adjusting the molecular weight, linkage abundance and glass transition temperature (Tg) of lignin macromolecules. As the anode material of LIBs, the prepared 3D flower-like LPCE70 could achieve a reversible capacity of 528 mAh g-1 at a current density of 0.2 A g-1 after 200 cycles, 63 % higher than that of commercial graphite. Furthermore, kinetic calculations of lithium-ion storage behavior of LPCs were firstly used to confirm the contribution ratio of diffusion-controlled behavior and capacitive effect. Lignin with a high linkage abundance could yield LPCE70 with the largest interlayer spacing and specific surface area to maximize lithium-ion storage from both diffusion-controlled and capacitive contributions of specific capacities. This work provides a green, facile and effective pathway for value-added utilization of lignin in LIBs.

Serum Long Noncoding RNA H19 and CKD Progression in IgA Nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is one of the most common primary glomerular diseases worldwide, especially in young Asian adults. Long RNA H19 is associated with renal pathologies, such as renal cell injury; however, a connection between serum H19 expression and kidney disease progression has not been demonstrated. METHOD: Our cohort consisted of 204 patients with IgAN. Serum H19 levels were determined with reverse-transcription quantitative polymerase between 1 May, 2014 and 1 May, 2015. H19 levels were log-transformed and categorical variables were categorized according to cutoff points of a ROC curve. Restricted cubic spline and generalized estimating equation analyses were performed to determine the association between serum H19 and kidney disease progression. RESULTS: H19 expression was significantly downregulated in patients with IgAN compared to healthy controls. Restricted cubic spline analyses showed that the relationship was negatively and linearly correlated (P for nonlinearly = 0.256). After adjusting for other potential clinical, pathologic, and treatment factors, H19 was found to be a protective factor for prognosis in IgAN (HR, 0.52; 95% CI 0.32-0.84; P = 0.008). ROC curve analysis showed that the clinical value of lncRNA H19 with CKD and area under the ROC curve was 0.746 (95% CI 0.663-0.829; P < 0.001) of the clinical prognostic value of H19. Serum restricted cubic spline analyses showed that the relationship was negatively and linearly correlated (P for non-linearly = 0.256). H19 > 0.097 in patients in IgAN was associated with a reduction of the risk of kidney progression by approximately 70% within 5 years compared to H19≤0.097 (HR, 0.30;95% CI 0.12-0.74; P = 0.009). CONCLUSION: H19 is an independent protective factor, and a high level of H19 often indicates better renal outcome within 5 years.

Fractionation of technical lignin and its application on the lignin/poly-(butylene adipate-co-terephthalate) bio-composites.

Complex and heterogeneous structures of lignin impede its further conversion and valorization. Herein, three technical lignins (from softwood, hardwood, and grass) were fractionated with acetone solvent to reduce their structural heterogeneity, which were then blended with poly-(butylene adipate-co-terephthalate) (PBAT) to fabricate biodegradable bio-composites. Macromolecular structures of lignins and their effects on the properties of lignin/PBAT composites were thoroughly investigated. Results showed that all fractionated lignin composites displayed better properties. Particularly, the raw and fractionated softwood lignin-based composites exhibited superior performance compared with others. Benefiting from the lower molecular weight, hydroxyl groups, and condensation, acetone fractionated softwood lignin presented the lowest Tg (115.7 °C), achieving ideal melt miscibility and interfacial interaction between lignin and PBAT. The decreased Tg of lignin facilitated the lignin dispersion in the matrix and increase the mechanical strength of the composites. Overall, the fractionated technical lignin possessed desirable physical and chemical structure features, conferring composites good miscibility and mechanical properties.

Clinical outcomes of EGFR+/METamp+ vs. EGFR+/METamp- untreated patients with advanced non-small cell lung cancer.

BACKGROUND: MET dysregulation has been implicated in the development of primary and secondary resistance to EGFR tyrosine kinase inhibitor (TKI) therapy. However, the clinicopathological characteristics and outcomes of patients harboring EGFR-sensitive mutations and de novo MET amplifications still need to be explored. METHODS: A total of 54 patients from our hospital with non-small cell lung cancer harboring EGFR-sensitive mutations and/or de novo MET amplifications were included in this study. Survival rates were estimated by the Kaplan-Meier method with log-rank statistics. Lung cancer organoids (LCOs) were generated from patient-derived malignant pleural effusion to perform drug sensitivity assays. RESULTS: Fifty-four patients with the appropriate clinicopathological characteristics were enrolled. MET FISH was performed in 40 patients who were stratified accordingly into two groups: EGFR+/METamp- (n = 22) and EGFR+/METamp + (n = 18). Survival rates for EGFR+/METamp- and EGFR+/METamp + patients respectively, were as follows: the median progression-free survival (PFS) was 12.1 and 1.9 months (p<0.001); the median post-progression overall survival (pOS) was 25.6 and 11.6 months (p = 0.023); the median overall survival (OS) was 33.2 and 12.7 months (p = 0.013). Drug testing conducted in LCOs derived from malignant pleural effusion from EGFR+/METamp + patients showed that dual targeted therapy was more effective than TKI monotherapy. CONCLUSION: EGFR+/METamp + patients treated with first-line TKI monotherapy had poor clinical outcomes. Dual targeted therapy showed potent anticancer activity in the LCO drug testing assay, suggesting that it is a promising first-line treatment for EGFR+/METamp + patients. Randomized controlled trials are needed to further validate these results.

Dual-Channel Fluorescent Probe for the Simultaneous Monitoring of Peroxynitrite and Adenosine-5'-triphosphate in Cellular Applications.

Changes in adenosine triphosphate (ATP) and peroxynitrite (ONOO-) concentrations have been correlated in a number of diseases including ischemia-reperfusion injury and drug-induced liver injury. Herein, we report the development of a fluorescent probe ATP-LW, which enables the simultaneous detection of ONOO- and ATP. ONOO- selectively oxidizes the boronate pinacol ester of ATP-LW to afford the fluorescent 4-hydroxy-1,8-naphthalimide product NA-OH (λex = 450 nm, λem = 562 nm or λex = 488 nm, λem = 568 nm). In contrast, the binding of ATP to ATP-LW induces the spirolactam ring opening of rhodamine to afford a highly emissive product (λex = 520 nm, λem = 587 nm). Due to the differences in emission between the ONOO- and ATP products, ATP-LW allows ONOO- levels to be monitored in the green channel (λex = 488 nm, λem = 500-575 nm) and ATP concentrations in the red channel (λex = 514 nm, λem = 575-650 nm). The use of ATP-LW as a combined ONOO- and ATP probe was demonstrated using hepatocytes (HL-7702 cells) in cellular imaging experiments. Treatment of HL-7702 cells with oligomycin A (an inhibitor of ATP synthase) resulted in a reduction of signal intensity in the red channel and an increase in that of the green channel as expected for a reduction in ATP concentrations. Similar fluorescence changes were seen in the presence of SIN-1 (an exogenous ONOO- donor).

Microhematuria Enhances the Risks of Relapse and Renal Progression in Primary Membranous Nephropathy.

Objective: To determine whether there is an association between microhematuria and relapse or kidney disease progression in patients with primary membranous nephropathy (PMN). Methods: A cohort of 639 patients with biopsy-proven PMN from two centers was followed for a median of 40 months. The exposures were initial hematuria, time-averaged hematuria, and cumulative duration of hematuria. The outcomes were relapse and renal progression, which were defined by a 40% reduction in renal function or end-stage renal disease. Cox proportional hazards regression and competing risk analyses were performed to yield hazard ratios (HRs) and subdistribution hazard ratios (sHRs) with 95% confidence intervals (CIs). Sensitivity and interaction analyses were also performed. Results: After adjusting for confounders, a higher level of initial hematuria was associated with a 1.43 (95% CI, 1.15-1.78) greater hazard of relapse. Worsening hematuria remarkably increased the risk of short-term relapse (HR, 4.64; 3.29-6.54). Time-averaged hematuria (sHR, 1.35; 1.12-1.63) and cumulative duration of hematuria (sHR, 1.17; 1.02-1.34) were independent predictors of renal progression. Hematuria remission was related to a reduced risk of renal progression over time in patients with positive microhematuria (sHR, 0.63; 0.41-0.96). Conclusions: A higher level of initial hematuria was a remarkable predictor of relapse in patients with PMN, and the magnitude and persistence of microhematuria were independently associated with kidney disease progression.

Clinical Outcomes of Patients With Primary Membranous Nephropathy and Subnephrotic Proteinuria.

Objectives: To update the information about the prognosis of patients with primary membranous nephropathy (MN) and subnephrotic proteinuria and identify the relevant predictors. Methods: In total, 474 cases of biopsy-proven primary MN with at least 18 months of follow-up were reviewed to determine the outcomes of the subgroup of patients that presented with subnephrotic proteinuria. Clinical data included initial proteinuria and microhematuria, defined as the average proteinuria/microhematuria of the first 6 months during the course. Outcomes included partial remission (PR), complete remission (CR), nephrotic proteinuria progression, and kidney function progression, defined as ≥50% loss of kidney function or end-stage kidney disease. Results: In total, 205 patients with primary MN and subnephrotic proteinuria at biopsy were eligible. During a median follow-up of 43 months, 200 (97.56%), 167 (81.46%), and 53 (25.85%) patients attained PR, CR, and nephrotic proteinuria progression, respectively. Only one patient (0.49%) progressed to the kidney function progression. By multivariate Cox hazards regression analyses, the initial proteinuria was identified as the independent predictor for PR, CR, and nephrotic proteinuria progression with adjusted hazard ratios (aHRs) of 0.67 (95% confidence interval, 0.56-0.80), 0.50 (95% CI, 0.40-0.63), and 2.97 (95% CI, 2.23-3.97), respectively. A higher level of initial microhematuria was also associated with an increased risk of nephrotic proteinuria progression. The corresponding aHR was 1.11 (95% CI, 1.05-1.17). Conclusion: Among patients with primary MN and subnephrotic proteinuria, although the overall prognosis is excellent, dynamic detection and effective management of proteinuria remain important. In addition, initial microhematuria may be another predictor of nephrotic proteinuria progression.

Differential Expression of Non-Coding RNA Signatures in Thyroid Cancer between Two Ethnic Groups.

Filipino Americans show higher thyroid cancer recurrence rates compared to European Americans. Although they are likely to die of this malignancy, the molecular mechanism has not yet been determined. Recent studies demonstrated that small non-coding RNAs could be utilized to assess thyroid cancer prognosis in tumor models. The goal of this study is to determine whether microRNA (miRNA) signatures are differentially expressed in thyroid cancer in two different ethnic groups. We also determined whether these miRNA signatures are related to cancer staging. This is a retrospective study of archival samples from patients with thyroid cancer (both sexes) in the pathology division from the last ten years at Loma Linda University School of Medicine, California. Deidentified patient demographics were extracted from the patient chart. Discarded formalin-fixed paraffin-embedded tissues were collected post-surgeries. We determined the differential expressions of microRNA in archival samples from Filipino Americans compared to European Americans using the state-of-the-art technique, HiSeq4000. By ingenuity pathway analysis, we determined miRNA targets and the pathways that those targets are involved in. We validated their expressions by real-time quantitative PCR and correlated them with the clinicopathological status in a larger cohort of miRNA samples from both ethnicities. We identified the differentially upregulated/downregulated miRNA clusters in Filipino Americans compared to European Americans. Some of these miRNA clusters are known to target genes that are linked to cancer invasion and metastasis. In univariate analysis, ethnicity and tumor staging were significant factors predicting miR-4633-5p upregulation. When including these factors in a multivariate logistic regression model, ethnicity and tumor staging remained significant independent predictors of miRNA upregulation, whereas the interaction of ethnicity and tumor staging was not significant. In contrast, ethnicity remained an independent predictor of significantly downregulated miR-491-5p and let-7 family. We provide evidence that Filipino Americans showed differentially expressed tumor-tissue-derived microRNA clusters. The functional implications of these miRNAs are under investigation.

Let-7i Reduces Aggressive Phenotype and Induces BRCAness in Ovarian Cancer Cells.

High-grade serous carcinoma of the ovary is a deadly gynecological cancer with poor long-term survival. Dysregulation of microRNAs has been shown to contribute to the formation of cancer stem cells (CSCs), an important part of oncogenesis and tumor progression. The let-7 family of microRNAs has previously been shown to regulate stemness and has tumor suppressive actions in a variety of cancers, including ovarian. Here, we demonstrate tumor suppressor actions of let-7i: repression of cancer cell stemness, inhibition of migration and invasion, and promotion of apoptosis, features important for cancer progression, relapse, and metastasis. Let-7i over-expression results in increased sensitivity to the PARP inhibitor olaparib in samples without BRCA mutations, consistent with induction of BRCAness phenotype. We also show that let-7i inhibits the expression of several factors involved in the homologous recombination repair (HRR) pathway, providing potential mechanisms by which the BRCAness phenotype could be induced. These actions of let-7i add to the rationale for use of this miRNA as a treatment for ovarian cancer patients, including those without mutations in the HRR pathway.